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ModernModern treatmenttreatment of of pancreaticpancreatic cancercancer 2009 2009 updateupdate
Morten LadekarlDepartment of Oncology
Aarhus University HospitalDenmark
Resectable diseaseLocally advanced diseaseAdvanced disease
Supportive carePancreatic neuro-endocrine tumours
RESECTABLE DISEASE
Disease stage 5-year survival ()
Localized 152
Regional 68
Distant 18
SEER Cancer Statistics Review 1975-2001
RESECTABLE DISEASE
CONKOCONKO--001001 Gem Gem vsvs observationobservation
RESECTABLE DISEASE
Significant increase in median survival from Significant increase in median survival from 20 to 2320 to 23 monthsmonthsIncrease in est 5Increase in est 5--year survival rate from year survival rate from 9 to 219 to 21Beneficial effect in all subgroupsBeneficial effect in all subgroups
Oettle et al JAMA 2007 amp Neuhaus et al ASCO proceedings 2008
ESPACESPAC‐‐33ESPAC‐3 A multicenter international open‐label randomized controlled
phase
III trial
of adjuvant
5‐fluorouracilfolinic
acid
(5‐FUFA) versus gemcitabine
(GEM) in patients with
resected
pancreatic
ductal
adenocarcinoma
Neoptolemos
et al
ASCO 2009
Gemcitabin
1 gang om ugen i
6 cyklusN=537
5FU+ folinsyre
i 5 dage hver
28 dag i 6 cyklusN=551
1088 pt
RESECTABLE DISEASE
3 arm BSC lukket pr3 arm BSC lukket praeligaeligmaturt grundet signifikant effekt af Gem maturt grundet signifikant effekt af Gem vsvs BSCBSCR0R1 R0R1 resektionresektion lt 8 uger efter operationlt 8 uger efter operation
ESPACESPAC‐‐33ESPAC‐3 A multicenter international open‐label randomized controlled
phase
III trial
of adjuvant
5‐fluorouracilfolinic
acid
(5‐FUFA) versus gemcitabine
(GEM) in patients with
resected
pancreatic
ductal
adenocarcinoma
Neoptolemos
et al
RESECTABLE DISEASE
News 2009 News 2009 adjuvantadjuvant treatmenttreatment
bullbull Gem Gem ogog 5FU 5FU erer ligelige effektiveeffektive men Gem men Gem erer mindstmindst toksisktoksisk
bullbull GemCapGemCap
vs Gem er i fase III (ESPACvs Gem er i fase III (ESPAC‐‐4)4)
RESECTABLE DISEASE
LOCALLY ADVANCED DISEASELOCALLY ADVANCED DISEASE
OptionsOptions
bullbull ChemotherapyChemotherapyndashndash GemGemndashndash Gem in combinationsGem in combinations
bullbull ChemoradiotherapyChemoradiotherapy
LOCALLY ADVANCED DISEASE
Overall survival on GemOverall survival on Gem
Storinolo et al Cancer 1998
LOCALLY ADVANCED DISEASE
ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT
LOCALLY ADVANCED DISEASE
LOCALLY ADVANCED DISEASE
ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT
LOCALLY ADVANCED DISEASE
LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT
LOCALLY ADVANCED DISEASE
LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT
LOCALLY ADVANCED DISEASE
Wilkowski
et al Final analysis
of a multicenter randomized
phase
II trial
comparing
three
different
chemoradiotherapy
regimens
in the treatment
of patients with
locally
advanced nonmetastatic
pancreatic
cancer ASCO 2009
Cis‐gemDag 1 8 22 29
Og cis‐gem
efter KRT
Kontinuerlig 5FU
Cis‐gemDag 18 22 2995 pt
ndashndash 3 forskellige kemo3 forskellige kemo‐‐regimer med regimer med konkomittantkonkomittant
strstraringaringlebehandling lebehandling aacuteaacute 50GY25fr 50GY25fr
LOCALLY ADVANCED DISEASE
Final analysis
of a multicenter randomized
phase
II trial
comparing
three
different
chemoradiotherapy
regimens
in the
treatment
of patients with
locally
advanced nonmetastatic
pancreatic
cancer Ralf
Wilkowski
bull 18 patienter blev opereret Fordeling ukendtbull Hoslashjere frekvens af grad 34 haeligmotologiske
bivirkninger i GC armene
bull Ingen forskel mellem 5FU og GemCis
PFSPFS((mdrmdr))
OSOS((mdrmdr))
HHaeligaeligmtoxmtox DiarreDiarre
RKTRKT--5FU5FU 44 9696 ++RKTRKT--GCGC 5656 9393 ++RKTRKT--GC + GCGC + GC 66 7373 ++
LOCALLY ADVANCED DISEASE
KonklusionerKonklusioner
bullbull StadigStadig ikkeikke afklaretafklaret omom kemokemo--radioterapiradioterapi forlforlaeligaeligngernger overlevelsenoverlevelsen i i forholdforhold tiltil kemoterapikemoterapi alenealene
bullbull IkkeIkke afklaretafklaret hvilkenhvilken kemoterapikemoterapi derder erer bedstbedst sammensammen med med radioterapiradioterapi
bullbull KemoKemo--radioterapiradioterapi kankan i i udvalgteudvalgte tilftilfaeligaeligldelde medfmedfoslashoslashrere konverteringkonvertering afaf sygdomsygdom frafra ikkeikke--resektabelresektabel tiltil resektabelresektabel men men detdet kankan kemoterapikemoterapi alenealene ogsogsaringaring
LOCALLY ADVANCED DISEASE
Herrmann 2008
LOCALLY ADVANCED DISEASE
ADVANCED DISEASEADVANCED DISEASE
AdvancedAdvanced diseasedisease
bullbull Median Median survivalsurvival untreateduntreated 33--4 4 monthsmonthsbullbull PrimaryPrimary goalsgoals of of treatmenttreatment
ndashndash Prolongation of Prolongation of survivalsurvivalndashndash ImprovementImprovement in in QoLQoL
ADVANCED DISEASE
GemcitabineGemcitabine vs 5vs 5--FUFU
Burris H et al J Clin Oncol 1997152403-2413
Gemcitabine 5-FU P
Clinical benefit response 24 5 0002 Median survival (months) 57 44 0002 Time to progression (months) 21 09 0001 6-month survival 46 31 1-year survival 18 2 Partial response 54 0 Stable disease 393 19 Composite of measurements of pain (analgesic consumption and pain intensity) Karnofsky
performance status and weight
ADVANCED DISEASE
SurvivalSurvival of of GemGem--treatedtreated patients patients accordingaccording to performance statusto performance status
Storinolo et al Cancer 1998
ADVANCED DISEASE
Combination chemotherapyCombination chemotherapy GemGem--CapCap
JCO october 2009
ADVANCED DISEASE
CunninghamCunningham et al GEMet al GEM--CAPCAP
Hazard ratio 080 95 CI 065ndash098Log-rank p=0026
Eur J Cancer Suppl 2005
Interim analysis 2005Final analysis 2009
ADVANCED DISEASE
MetaMeta--analysisanalysis of GEMof GEM--CAPCAP
Cunningham et al JCO 2009
ADVANCED DISEASE
Gem vs Gem vs GemGem‐‐platinumplatinumDi Miao A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
ASCO 2009
Gemcitabin
som kontrol +
cisplatin
ugentlig 25mgm2N=201
Gemcitabin
ugentlig i 7 uger
2 ugers pause og dag 18 15 i
4 ugers cyklusN=199
400 pt
ADVANCED DISEASE
GemGem GemCisGemCis
OSOS11‐‐year year survivalsurvivalPFSPFS
AnAnaeligaeligmimiTrombocytopeniTrombocytopeni
83 mdr 83 mdr 340 340 39 mdr 39 mdr
39392929
72 mdr 72 mdr 307 307 38 mdr38 mdr
50505757
A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma
The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
Di Miao
bull Alle endepunkter insignifikantebull Subgruppeanalyse
af PS 0 Signifikant negativ effekt
bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant
efter inklusion af dette studium
ADVANCED DISEASE
CombinationCombination chemotherapychemotherapy and and effecteffect accordingaccording to to performance statusperformance status
Heinemann et al BMC Cancer 2008
ADVANCED DISEASE
PA3 study GemPA3 study Gem--erlotiniberlotinib Overall survivalOverall survival
10090807060504030201
0
Surv
ival
pro
babi
lity
0 6 12 18 24Survival (months)
Tarcevatrade gemcitabine
(n=285)
Placebo gemcitabine
(n=284)
Median survival (months) 637 591
1-year survival 24 17
HR=079 (95 CI 066-095) P=0011 (adjusted for PS and extent of disease at randomization)
TarcevaTM + gemcitabinePlacebo + gemcitabine
Moore et al JCO 2007
ADVANCED DISEASE
PA3 studyPA3 study Hazard ratios for survivalHazard ratios for survival
HR 95 CI n
Tarcevaplacebo
Performance status 0-1Performance status 2
Locally advancedDistant metastasis
Pain 20 Pain gt20
MaleFemale
Age lt65Age 65
United StatesCanada
Rest of World
HER1EGFR positiveHER1EGFR negative
HER1EGFR unknown
1
082 07-10 569
087 07-11 463056 04-08 106
094 06-14 138078 06-09 431
070 05-09 258098 08-13 296
074 06-09 298096 07-13 271
074 06-10 301093 07-12 268
071 05-09 211079 05-12 117096 07-13 241
073 04-12 74077 05-13 71086 07-11 424
Fact
ors
Moore et al JCO 2007
ADVANCED DISEASE
Events
Tarceva () n=282
Placebo () n=280
Any Grade 34 Any Grade 34Rash 72 6 29 1Diarrhoea 56 6 41 2Infection 43 17 34 16Stomatitis 23 lt1 14 0Pneumonitis 2 2 1 lt1Fatigue 89 15 86 15
PA3 studyPA3 study Adverse eventsAdverse events
Moore et al JCO 2007
ADVANCED DISEASE
AccetableAccetable standard standard systemicsystemic treatmenttreatment options 2009options 2009
bullbull GEM GEM alonealonebullbull GEMGEM--erlotiniberlotinib
ndashndash registredregistred for for metastaticmetastatic PC PC onlyonly mOSmOS + 12 + 12 daysdays somesome additionaladditional toxicitytoxicity
bullbull GEMGEM--CAP CAP mOSmOS + 1 + 1 monthmonth onlyonly significantsignificant in in metameta--analysisanalysis
bullbull GEMGEM--platinumplatinum ndashndash doubtfuldoubtful effecteffect -- nownow not not significantsignificant in in metameta--
analysisanalysis significantsignificant toxicitytoxicity
ADVANCED DISEASE
SUPPORTIVE CARESUPPORTIVE CARE
Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer
SUPPORTIVE CARE
GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)
enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009
Baggrund
VTE forekommer hos ca 10 af patienter med PC
Formaringl
Undersoslashge effekt af LMWH (Klexane) i kombination med
kemoterapi mht frekvens af VTE og mOS
Inklusion
Avanceret PC ikke tidligere kemoterapi
Karnofsky
PS gt 60
Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor
2 aringr
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al ASCO 2009
Antal af VTE 15152 i observation ndash 2160 i LMWH
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al
Konklusion
LMWH er effektiv og sikker behandling til forebyggelse af
VTE hos patienter med pancreascancer
Endelige resultater paring
mOS og mTTP
afventes
SUPPORTIVE CARE
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
RESECTABLE DISEASE
Disease stage 5-year survival ()
Localized 152
Regional 68
Distant 18
SEER Cancer Statistics Review 1975-2001
RESECTABLE DISEASE
CONKOCONKO--001001 Gem Gem vsvs observationobservation
RESECTABLE DISEASE
Significant increase in median survival from Significant increase in median survival from 20 to 2320 to 23 monthsmonthsIncrease in est 5Increase in est 5--year survival rate from year survival rate from 9 to 219 to 21Beneficial effect in all subgroupsBeneficial effect in all subgroups
Oettle et al JAMA 2007 amp Neuhaus et al ASCO proceedings 2008
ESPACESPAC‐‐33ESPAC‐3 A multicenter international open‐label randomized controlled
phase
III trial
of adjuvant
5‐fluorouracilfolinic
acid
(5‐FUFA) versus gemcitabine
(GEM) in patients with
resected
pancreatic
ductal
adenocarcinoma
Neoptolemos
et al
ASCO 2009
Gemcitabin
1 gang om ugen i
6 cyklusN=537
5FU+ folinsyre
i 5 dage hver
28 dag i 6 cyklusN=551
1088 pt
RESECTABLE DISEASE
3 arm BSC lukket pr3 arm BSC lukket praeligaeligmaturt grundet signifikant effekt af Gem maturt grundet signifikant effekt af Gem vsvs BSCBSCR0R1 R0R1 resektionresektion lt 8 uger efter operationlt 8 uger efter operation
ESPACESPAC‐‐33ESPAC‐3 A multicenter international open‐label randomized controlled
phase
III trial
of adjuvant
5‐fluorouracilfolinic
acid
(5‐FUFA) versus gemcitabine
(GEM) in patients with
resected
pancreatic
ductal
adenocarcinoma
Neoptolemos
et al
RESECTABLE DISEASE
News 2009 News 2009 adjuvantadjuvant treatmenttreatment
bullbull Gem Gem ogog 5FU 5FU erer ligelige effektiveeffektive men Gem men Gem erer mindstmindst toksisktoksisk
bullbull GemCapGemCap
vs Gem er i fase III (ESPACvs Gem er i fase III (ESPAC‐‐4)4)
RESECTABLE DISEASE
LOCALLY ADVANCED DISEASELOCALLY ADVANCED DISEASE
OptionsOptions
bullbull ChemotherapyChemotherapyndashndash GemGemndashndash Gem in combinationsGem in combinations
bullbull ChemoradiotherapyChemoradiotherapy
LOCALLY ADVANCED DISEASE
Overall survival on GemOverall survival on Gem
Storinolo et al Cancer 1998
LOCALLY ADVANCED DISEASE
ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT
LOCALLY ADVANCED DISEASE
LOCALLY ADVANCED DISEASE
ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT
LOCALLY ADVANCED DISEASE
LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT
LOCALLY ADVANCED DISEASE
LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT
LOCALLY ADVANCED DISEASE
Wilkowski
et al Final analysis
of a multicenter randomized
phase
II trial
comparing
three
different
chemoradiotherapy
regimens
in the treatment
of patients with
locally
advanced nonmetastatic
pancreatic
cancer ASCO 2009
Cis‐gemDag 1 8 22 29
Og cis‐gem
efter KRT
Kontinuerlig 5FU
Cis‐gemDag 18 22 2995 pt
ndashndash 3 forskellige kemo3 forskellige kemo‐‐regimer med regimer med konkomittantkonkomittant
strstraringaringlebehandling lebehandling aacuteaacute 50GY25fr 50GY25fr
LOCALLY ADVANCED DISEASE
Final analysis
of a multicenter randomized
phase
II trial
comparing
three
different
chemoradiotherapy
regimens
in the
treatment
of patients with
locally
advanced nonmetastatic
pancreatic
cancer Ralf
Wilkowski
bull 18 patienter blev opereret Fordeling ukendtbull Hoslashjere frekvens af grad 34 haeligmotologiske
bivirkninger i GC armene
bull Ingen forskel mellem 5FU og GemCis
PFSPFS((mdrmdr))
OSOS((mdrmdr))
HHaeligaeligmtoxmtox DiarreDiarre
RKTRKT--5FU5FU 44 9696 ++RKTRKT--GCGC 5656 9393 ++RKTRKT--GC + GCGC + GC 66 7373 ++
LOCALLY ADVANCED DISEASE
KonklusionerKonklusioner
bullbull StadigStadig ikkeikke afklaretafklaret omom kemokemo--radioterapiradioterapi forlforlaeligaeligngernger overlevelsenoverlevelsen i i forholdforhold tiltil kemoterapikemoterapi alenealene
bullbull IkkeIkke afklaretafklaret hvilkenhvilken kemoterapikemoterapi derder erer bedstbedst sammensammen med med radioterapiradioterapi
bullbull KemoKemo--radioterapiradioterapi kankan i i udvalgteudvalgte tilftilfaeligaeligldelde medfmedfoslashoslashrere konverteringkonvertering afaf sygdomsygdom frafra ikkeikke--resektabelresektabel tiltil resektabelresektabel men men detdet kankan kemoterapikemoterapi alenealene ogsogsaringaring
LOCALLY ADVANCED DISEASE
Herrmann 2008
LOCALLY ADVANCED DISEASE
ADVANCED DISEASEADVANCED DISEASE
AdvancedAdvanced diseasedisease
bullbull Median Median survivalsurvival untreateduntreated 33--4 4 monthsmonthsbullbull PrimaryPrimary goalsgoals of of treatmenttreatment
ndashndash Prolongation of Prolongation of survivalsurvivalndashndash ImprovementImprovement in in QoLQoL
ADVANCED DISEASE
GemcitabineGemcitabine vs 5vs 5--FUFU
Burris H et al J Clin Oncol 1997152403-2413
Gemcitabine 5-FU P
Clinical benefit response 24 5 0002 Median survival (months) 57 44 0002 Time to progression (months) 21 09 0001 6-month survival 46 31 1-year survival 18 2 Partial response 54 0 Stable disease 393 19 Composite of measurements of pain (analgesic consumption and pain intensity) Karnofsky
performance status and weight
ADVANCED DISEASE
SurvivalSurvival of of GemGem--treatedtreated patients patients accordingaccording to performance statusto performance status
Storinolo et al Cancer 1998
ADVANCED DISEASE
Combination chemotherapyCombination chemotherapy GemGem--CapCap
JCO october 2009
ADVANCED DISEASE
CunninghamCunningham et al GEMet al GEM--CAPCAP
Hazard ratio 080 95 CI 065ndash098Log-rank p=0026
Eur J Cancer Suppl 2005
Interim analysis 2005Final analysis 2009
ADVANCED DISEASE
MetaMeta--analysisanalysis of GEMof GEM--CAPCAP
Cunningham et al JCO 2009
ADVANCED DISEASE
Gem vs Gem vs GemGem‐‐platinumplatinumDi Miao A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
ASCO 2009
Gemcitabin
som kontrol +
cisplatin
ugentlig 25mgm2N=201
Gemcitabin
ugentlig i 7 uger
2 ugers pause og dag 18 15 i
4 ugers cyklusN=199
400 pt
ADVANCED DISEASE
GemGem GemCisGemCis
OSOS11‐‐year year survivalsurvivalPFSPFS
AnAnaeligaeligmimiTrombocytopeniTrombocytopeni
83 mdr 83 mdr 340 340 39 mdr 39 mdr
39392929
72 mdr 72 mdr 307 307 38 mdr38 mdr
50505757
A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma
The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
Di Miao
bull Alle endepunkter insignifikantebull Subgruppeanalyse
af PS 0 Signifikant negativ effekt
bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant
efter inklusion af dette studium
ADVANCED DISEASE
CombinationCombination chemotherapychemotherapy and and effecteffect accordingaccording to to performance statusperformance status
Heinemann et al BMC Cancer 2008
ADVANCED DISEASE
PA3 study GemPA3 study Gem--erlotiniberlotinib Overall survivalOverall survival
10090807060504030201
0
Surv
ival
pro
babi
lity
0 6 12 18 24Survival (months)
Tarcevatrade gemcitabine
(n=285)
Placebo gemcitabine
(n=284)
Median survival (months) 637 591
1-year survival 24 17
HR=079 (95 CI 066-095) P=0011 (adjusted for PS and extent of disease at randomization)
TarcevaTM + gemcitabinePlacebo + gemcitabine
Moore et al JCO 2007
ADVANCED DISEASE
PA3 studyPA3 study Hazard ratios for survivalHazard ratios for survival
HR 95 CI n
Tarcevaplacebo
Performance status 0-1Performance status 2
Locally advancedDistant metastasis
Pain 20 Pain gt20
MaleFemale
Age lt65Age 65
United StatesCanada
Rest of World
HER1EGFR positiveHER1EGFR negative
HER1EGFR unknown
1
082 07-10 569
087 07-11 463056 04-08 106
094 06-14 138078 06-09 431
070 05-09 258098 08-13 296
074 06-09 298096 07-13 271
074 06-10 301093 07-12 268
071 05-09 211079 05-12 117096 07-13 241
073 04-12 74077 05-13 71086 07-11 424
Fact
ors
Moore et al JCO 2007
ADVANCED DISEASE
Events
Tarceva () n=282
Placebo () n=280
Any Grade 34 Any Grade 34Rash 72 6 29 1Diarrhoea 56 6 41 2Infection 43 17 34 16Stomatitis 23 lt1 14 0Pneumonitis 2 2 1 lt1Fatigue 89 15 86 15
PA3 studyPA3 study Adverse eventsAdverse events
Moore et al JCO 2007
ADVANCED DISEASE
AccetableAccetable standard standard systemicsystemic treatmenttreatment options 2009options 2009
bullbull GEM GEM alonealonebullbull GEMGEM--erlotiniberlotinib
ndashndash registredregistred for for metastaticmetastatic PC PC onlyonly mOSmOS + 12 + 12 daysdays somesome additionaladditional toxicitytoxicity
bullbull GEMGEM--CAP CAP mOSmOS + 1 + 1 monthmonth onlyonly significantsignificant in in metameta--analysisanalysis
bullbull GEMGEM--platinumplatinum ndashndash doubtfuldoubtful effecteffect -- nownow not not significantsignificant in in metameta--
analysisanalysis significantsignificant toxicitytoxicity
ADVANCED DISEASE
SUPPORTIVE CARESUPPORTIVE CARE
Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer
SUPPORTIVE CARE
GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)
enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009
Baggrund
VTE forekommer hos ca 10 af patienter med PC
Formaringl
Undersoslashge effekt af LMWH (Klexane) i kombination med
kemoterapi mht frekvens af VTE og mOS
Inklusion
Avanceret PC ikke tidligere kemoterapi
Karnofsky
PS gt 60
Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor
2 aringr
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al ASCO 2009
Antal af VTE 15152 i observation ndash 2160 i LMWH
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al
Konklusion
LMWH er effektiv og sikker behandling til forebyggelse af
VTE hos patienter med pancreascancer
Endelige resultater paring
mOS og mTTP
afventes
SUPPORTIVE CARE
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
Disease stage 5-year survival ()
Localized 152
Regional 68
Distant 18
SEER Cancer Statistics Review 1975-2001
RESECTABLE DISEASE
CONKOCONKO--001001 Gem Gem vsvs observationobservation
RESECTABLE DISEASE
Significant increase in median survival from Significant increase in median survival from 20 to 2320 to 23 monthsmonthsIncrease in est 5Increase in est 5--year survival rate from year survival rate from 9 to 219 to 21Beneficial effect in all subgroupsBeneficial effect in all subgroups
Oettle et al JAMA 2007 amp Neuhaus et al ASCO proceedings 2008
ESPACESPAC‐‐33ESPAC‐3 A multicenter international open‐label randomized controlled
phase
III trial
of adjuvant
5‐fluorouracilfolinic
acid
(5‐FUFA) versus gemcitabine
(GEM) in patients with
resected
pancreatic
ductal
adenocarcinoma
Neoptolemos
et al
ASCO 2009
Gemcitabin
1 gang om ugen i
6 cyklusN=537
5FU+ folinsyre
i 5 dage hver
28 dag i 6 cyklusN=551
1088 pt
RESECTABLE DISEASE
3 arm BSC lukket pr3 arm BSC lukket praeligaeligmaturt grundet signifikant effekt af Gem maturt grundet signifikant effekt af Gem vsvs BSCBSCR0R1 R0R1 resektionresektion lt 8 uger efter operationlt 8 uger efter operation
ESPACESPAC‐‐33ESPAC‐3 A multicenter international open‐label randomized controlled
phase
III trial
of adjuvant
5‐fluorouracilfolinic
acid
(5‐FUFA) versus gemcitabine
(GEM) in patients with
resected
pancreatic
ductal
adenocarcinoma
Neoptolemos
et al
RESECTABLE DISEASE
News 2009 News 2009 adjuvantadjuvant treatmenttreatment
bullbull Gem Gem ogog 5FU 5FU erer ligelige effektiveeffektive men Gem men Gem erer mindstmindst toksisktoksisk
bullbull GemCapGemCap
vs Gem er i fase III (ESPACvs Gem er i fase III (ESPAC‐‐4)4)
RESECTABLE DISEASE
LOCALLY ADVANCED DISEASELOCALLY ADVANCED DISEASE
OptionsOptions
bullbull ChemotherapyChemotherapyndashndash GemGemndashndash Gem in combinationsGem in combinations
bullbull ChemoradiotherapyChemoradiotherapy
LOCALLY ADVANCED DISEASE
Overall survival on GemOverall survival on Gem
Storinolo et al Cancer 1998
LOCALLY ADVANCED DISEASE
ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT
LOCALLY ADVANCED DISEASE
LOCALLY ADVANCED DISEASE
ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT
LOCALLY ADVANCED DISEASE
LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT
LOCALLY ADVANCED DISEASE
LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT
LOCALLY ADVANCED DISEASE
Wilkowski
et al Final analysis
of a multicenter randomized
phase
II trial
comparing
three
different
chemoradiotherapy
regimens
in the treatment
of patients with
locally
advanced nonmetastatic
pancreatic
cancer ASCO 2009
Cis‐gemDag 1 8 22 29
Og cis‐gem
efter KRT
Kontinuerlig 5FU
Cis‐gemDag 18 22 2995 pt
ndashndash 3 forskellige kemo3 forskellige kemo‐‐regimer med regimer med konkomittantkonkomittant
strstraringaringlebehandling lebehandling aacuteaacute 50GY25fr 50GY25fr
LOCALLY ADVANCED DISEASE
Final analysis
of a multicenter randomized
phase
II trial
comparing
three
different
chemoradiotherapy
regimens
in the
treatment
of patients with
locally
advanced nonmetastatic
pancreatic
cancer Ralf
Wilkowski
bull 18 patienter blev opereret Fordeling ukendtbull Hoslashjere frekvens af grad 34 haeligmotologiske
bivirkninger i GC armene
bull Ingen forskel mellem 5FU og GemCis
PFSPFS((mdrmdr))
OSOS((mdrmdr))
HHaeligaeligmtoxmtox DiarreDiarre
RKTRKT--5FU5FU 44 9696 ++RKTRKT--GCGC 5656 9393 ++RKTRKT--GC + GCGC + GC 66 7373 ++
LOCALLY ADVANCED DISEASE
KonklusionerKonklusioner
bullbull StadigStadig ikkeikke afklaretafklaret omom kemokemo--radioterapiradioterapi forlforlaeligaeligngernger overlevelsenoverlevelsen i i forholdforhold tiltil kemoterapikemoterapi alenealene
bullbull IkkeIkke afklaretafklaret hvilkenhvilken kemoterapikemoterapi derder erer bedstbedst sammensammen med med radioterapiradioterapi
bullbull KemoKemo--radioterapiradioterapi kankan i i udvalgteudvalgte tilftilfaeligaeligldelde medfmedfoslashoslashrere konverteringkonvertering afaf sygdomsygdom frafra ikkeikke--resektabelresektabel tiltil resektabelresektabel men men detdet kankan kemoterapikemoterapi alenealene ogsogsaringaring
LOCALLY ADVANCED DISEASE
Herrmann 2008
LOCALLY ADVANCED DISEASE
ADVANCED DISEASEADVANCED DISEASE
AdvancedAdvanced diseasedisease
bullbull Median Median survivalsurvival untreateduntreated 33--4 4 monthsmonthsbullbull PrimaryPrimary goalsgoals of of treatmenttreatment
ndashndash Prolongation of Prolongation of survivalsurvivalndashndash ImprovementImprovement in in QoLQoL
ADVANCED DISEASE
GemcitabineGemcitabine vs 5vs 5--FUFU
Burris H et al J Clin Oncol 1997152403-2413
Gemcitabine 5-FU P
Clinical benefit response 24 5 0002 Median survival (months) 57 44 0002 Time to progression (months) 21 09 0001 6-month survival 46 31 1-year survival 18 2 Partial response 54 0 Stable disease 393 19 Composite of measurements of pain (analgesic consumption and pain intensity) Karnofsky
performance status and weight
ADVANCED DISEASE
SurvivalSurvival of of GemGem--treatedtreated patients patients accordingaccording to performance statusto performance status
Storinolo et al Cancer 1998
ADVANCED DISEASE
Combination chemotherapyCombination chemotherapy GemGem--CapCap
JCO october 2009
ADVANCED DISEASE
CunninghamCunningham et al GEMet al GEM--CAPCAP
Hazard ratio 080 95 CI 065ndash098Log-rank p=0026
Eur J Cancer Suppl 2005
Interim analysis 2005Final analysis 2009
ADVANCED DISEASE
MetaMeta--analysisanalysis of GEMof GEM--CAPCAP
Cunningham et al JCO 2009
ADVANCED DISEASE
Gem vs Gem vs GemGem‐‐platinumplatinumDi Miao A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
ASCO 2009
Gemcitabin
som kontrol +
cisplatin
ugentlig 25mgm2N=201
Gemcitabin
ugentlig i 7 uger
2 ugers pause og dag 18 15 i
4 ugers cyklusN=199
400 pt
ADVANCED DISEASE
GemGem GemCisGemCis
OSOS11‐‐year year survivalsurvivalPFSPFS
AnAnaeligaeligmimiTrombocytopeniTrombocytopeni
83 mdr 83 mdr 340 340 39 mdr 39 mdr
39392929
72 mdr 72 mdr 307 307 38 mdr38 mdr
50505757
A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma
The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
Di Miao
bull Alle endepunkter insignifikantebull Subgruppeanalyse
af PS 0 Signifikant negativ effekt
bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant
efter inklusion af dette studium
ADVANCED DISEASE
CombinationCombination chemotherapychemotherapy and and effecteffect accordingaccording to to performance statusperformance status
Heinemann et al BMC Cancer 2008
ADVANCED DISEASE
PA3 study GemPA3 study Gem--erlotiniberlotinib Overall survivalOverall survival
10090807060504030201
0
Surv
ival
pro
babi
lity
0 6 12 18 24Survival (months)
Tarcevatrade gemcitabine
(n=285)
Placebo gemcitabine
(n=284)
Median survival (months) 637 591
1-year survival 24 17
HR=079 (95 CI 066-095) P=0011 (adjusted for PS and extent of disease at randomization)
TarcevaTM + gemcitabinePlacebo + gemcitabine
Moore et al JCO 2007
ADVANCED DISEASE
PA3 studyPA3 study Hazard ratios for survivalHazard ratios for survival
HR 95 CI n
Tarcevaplacebo
Performance status 0-1Performance status 2
Locally advancedDistant metastasis
Pain 20 Pain gt20
MaleFemale
Age lt65Age 65
United StatesCanada
Rest of World
HER1EGFR positiveHER1EGFR negative
HER1EGFR unknown
1
082 07-10 569
087 07-11 463056 04-08 106
094 06-14 138078 06-09 431
070 05-09 258098 08-13 296
074 06-09 298096 07-13 271
074 06-10 301093 07-12 268
071 05-09 211079 05-12 117096 07-13 241
073 04-12 74077 05-13 71086 07-11 424
Fact
ors
Moore et al JCO 2007
ADVANCED DISEASE
Events
Tarceva () n=282
Placebo () n=280
Any Grade 34 Any Grade 34Rash 72 6 29 1Diarrhoea 56 6 41 2Infection 43 17 34 16Stomatitis 23 lt1 14 0Pneumonitis 2 2 1 lt1Fatigue 89 15 86 15
PA3 studyPA3 study Adverse eventsAdverse events
Moore et al JCO 2007
ADVANCED DISEASE
AccetableAccetable standard standard systemicsystemic treatmenttreatment options 2009options 2009
bullbull GEM GEM alonealonebullbull GEMGEM--erlotiniberlotinib
ndashndash registredregistred for for metastaticmetastatic PC PC onlyonly mOSmOS + 12 + 12 daysdays somesome additionaladditional toxicitytoxicity
bullbull GEMGEM--CAP CAP mOSmOS + 1 + 1 monthmonth onlyonly significantsignificant in in metameta--analysisanalysis
bullbull GEMGEM--platinumplatinum ndashndash doubtfuldoubtful effecteffect -- nownow not not significantsignificant in in metameta--
analysisanalysis significantsignificant toxicitytoxicity
ADVANCED DISEASE
SUPPORTIVE CARESUPPORTIVE CARE
Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer
SUPPORTIVE CARE
GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)
enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009
Baggrund
VTE forekommer hos ca 10 af patienter med PC
Formaringl
Undersoslashge effekt af LMWH (Klexane) i kombination med
kemoterapi mht frekvens af VTE og mOS
Inklusion
Avanceret PC ikke tidligere kemoterapi
Karnofsky
PS gt 60
Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor
2 aringr
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al ASCO 2009
Antal af VTE 15152 i observation ndash 2160 i LMWH
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al
Konklusion
LMWH er effektiv og sikker behandling til forebyggelse af
VTE hos patienter med pancreascancer
Endelige resultater paring
mOS og mTTP
afventes
SUPPORTIVE CARE
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
CONKOCONKO--001001 Gem Gem vsvs observationobservation
RESECTABLE DISEASE
Significant increase in median survival from Significant increase in median survival from 20 to 2320 to 23 monthsmonthsIncrease in est 5Increase in est 5--year survival rate from year survival rate from 9 to 219 to 21Beneficial effect in all subgroupsBeneficial effect in all subgroups
Oettle et al JAMA 2007 amp Neuhaus et al ASCO proceedings 2008
ESPACESPAC‐‐33ESPAC‐3 A multicenter international open‐label randomized controlled
phase
III trial
of adjuvant
5‐fluorouracilfolinic
acid
(5‐FUFA) versus gemcitabine
(GEM) in patients with
resected
pancreatic
ductal
adenocarcinoma
Neoptolemos
et al
ASCO 2009
Gemcitabin
1 gang om ugen i
6 cyklusN=537
5FU+ folinsyre
i 5 dage hver
28 dag i 6 cyklusN=551
1088 pt
RESECTABLE DISEASE
3 arm BSC lukket pr3 arm BSC lukket praeligaeligmaturt grundet signifikant effekt af Gem maturt grundet signifikant effekt af Gem vsvs BSCBSCR0R1 R0R1 resektionresektion lt 8 uger efter operationlt 8 uger efter operation
ESPACESPAC‐‐33ESPAC‐3 A multicenter international open‐label randomized controlled
phase
III trial
of adjuvant
5‐fluorouracilfolinic
acid
(5‐FUFA) versus gemcitabine
(GEM) in patients with
resected
pancreatic
ductal
adenocarcinoma
Neoptolemos
et al
RESECTABLE DISEASE
News 2009 News 2009 adjuvantadjuvant treatmenttreatment
bullbull Gem Gem ogog 5FU 5FU erer ligelige effektiveeffektive men Gem men Gem erer mindstmindst toksisktoksisk
bullbull GemCapGemCap
vs Gem er i fase III (ESPACvs Gem er i fase III (ESPAC‐‐4)4)
RESECTABLE DISEASE
LOCALLY ADVANCED DISEASELOCALLY ADVANCED DISEASE
OptionsOptions
bullbull ChemotherapyChemotherapyndashndash GemGemndashndash Gem in combinationsGem in combinations
bullbull ChemoradiotherapyChemoradiotherapy
LOCALLY ADVANCED DISEASE
Overall survival on GemOverall survival on Gem
Storinolo et al Cancer 1998
LOCALLY ADVANCED DISEASE
ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT
LOCALLY ADVANCED DISEASE
LOCALLY ADVANCED DISEASE
ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT
LOCALLY ADVANCED DISEASE
LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT
LOCALLY ADVANCED DISEASE
LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT
LOCALLY ADVANCED DISEASE
Wilkowski
et al Final analysis
of a multicenter randomized
phase
II trial
comparing
three
different
chemoradiotherapy
regimens
in the treatment
of patients with
locally
advanced nonmetastatic
pancreatic
cancer ASCO 2009
Cis‐gemDag 1 8 22 29
Og cis‐gem
efter KRT
Kontinuerlig 5FU
Cis‐gemDag 18 22 2995 pt
ndashndash 3 forskellige kemo3 forskellige kemo‐‐regimer med regimer med konkomittantkonkomittant
strstraringaringlebehandling lebehandling aacuteaacute 50GY25fr 50GY25fr
LOCALLY ADVANCED DISEASE
Final analysis
of a multicenter randomized
phase
II trial
comparing
three
different
chemoradiotherapy
regimens
in the
treatment
of patients with
locally
advanced nonmetastatic
pancreatic
cancer Ralf
Wilkowski
bull 18 patienter blev opereret Fordeling ukendtbull Hoslashjere frekvens af grad 34 haeligmotologiske
bivirkninger i GC armene
bull Ingen forskel mellem 5FU og GemCis
PFSPFS((mdrmdr))
OSOS((mdrmdr))
HHaeligaeligmtoxmtox DiarreDiarre
RKTRKT--5FU5FU 44 9696 ++RKTRKT--GCGC 5656 9393 ++RKTRKT--GC + GCGC + GC 66 7373 ++
LOCALLY ADVANCED DISEASE
KonklusionerKonklusioner
bullbull StadigStadig ikkeikke afklaretafklaret omom kemokemo--radioterapiradioterapi forlforlaeligaeligngernger overlevelsenoverlevelsen i i forholdforhold tiltil kemoterapikemoterapi alenealene
bullbull IkkeIkke afklaretafklaret hvilkenhvilken kemoterapikemoterapi derder erer bedstbedst sammensammen med med radioterapiradioterapi
bullbull KemoKemo--radioterapiradioterapi kankan i i udvalgteudvalgte tilftilfaeligaeligldelde medfmedfoslashoslashrere konverteringkonvertering afaf sygdomsygdom frafra ikkeikke--resektabelresektabel tiltil resektabelresektabel men men detdet kankan kemoterapikemoterapi alenealene ogsogsaringaring
LOCALLY ADVANCED DISEASE
Herrmann 2008
LOCALLY ADVANCED DISEASE
ADVANCED DISEASEADVANCED DISEASE
AdvancedAdvanced diseasedisease
bullbull Median Median survivalsurvival untreateduntreated 33--4 4 monthsmonthsbullbull PrimaryPrimary goalsgoals of of treatmenttreatment
ndashndash Prolongation of Prolongation of survivalsurvivalndashndash ImprovementImprovement in in QoLQoL
ADVANCED DISEASE
GemcitabineGemcitabine vs 5vs 5--FUFU
Burris H et al J Clin Oncol 1997152403-2413
Gemcitabine 5-FU P
Clinical benefit response 24 5 0002 Median survival (months) 57 44 0002 Time to progression (months) 21 09 0001 6-month survival 46 31 1-year survival 18 2 Partial response 54 0 Stable disease 393 19 Composite of measurements of pain (analgesic consumption and pain intensity) Karnofsky
performance status and weight
ADVANCED DISEASE
SurvivalSurvival of of GemGem--treatedtreated patients patients accordingaccording to performance statusto performance status
Storinolo et al Cancer 1998
ADVANCED DISEASE
Combination chemotherapyCombination chemotherapy GemGem--CapCap
JCO october 2009
ADVANCED DISEASE
CunninghamCunningham et al GEMet al GEM--CAPCAP
Hazard ratio 080 95 CI 065ndash098Log-rank p=0026
Eur J Cancer Suppl 2005
Interim analysis 2005Final analysis 2009
ADVANCED DISEASE
MetaMeta--analysisanalysis of GEMof GEM--CAPCAP
Cunningham et al JCO 2009
ADVANCED DISEASE
Gem vs Gem vs GemGem‐‐platinumplatinumDi Miao A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
ASCO 2009
Gemcitabin
som kontrol +
cisplatin
ugentlig 25mgm2N=201
Gemcitabin
ugentlig i 7 uger
2 ugers pause og dag 18 15 i
4 ugers cyklusN=199
400 pt
ADVANCED DISEASE
GemGem GemCisGemCis
OSOS11‐‐year year survivalsurvivalPFSPFS
AnAnaeligaeligmimiTrombocytopeniTrombocytopeni
83 mdr 83 mdr 340 340 39 mdr 39 mdr
39392929
72 mdr 72 mdr 307 307 38 mdr38 mdr
50505757
A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma
The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
Di Miao
bull Alle endepunkter insignifikantebull Subgruppeanalyse
af PS 0 Signifikant negativ effekt
bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant
efter inklusion af dette studium
ADVANCED DISEASE
CombinationCombination chemotherapychemotherapy and and effecteffect accordingaccording to to performance statusperformance status
Heinemann et al BMC Cancer 2008
ADVANCED DISEASE
PA3 study GemPA3 study Gem--erlotiniberlotinib Overall survivalOverall survival
10090807060504030201
0
Surv
ival
pro
babi
lity
0 6 12 18 24Survival (months)
Tarcevatrade gemcitabine
(n=285)
Placebo gemcitabine
(n=284)
Median survival (months) 637 591
1-year survival 24 17
HR=079 (95 CI 066-095) P=0011 (adjusted for PS and extent of disease at randomization)
TarcevaTM + gemcitabinePlacebo + gemcitabine
Moore et al JCO 2007
ADVANCED DISEASE
PA3 studyPA3 study Hazard ratios for survivalHazard ratios for survival
HR 95 CI n
Tarcevaplacebo
Performance status 0-1Performance status 2
Locally advancedDistant metastasis
Pain 20 Pain gt20
MaleFemale
Age lt65Age 65
United StatesCanada
Rest of World
HER1EGFR positiveHER1EGFR negative
HER1EGFR unknown
1
082 07-10 569
087 07-11 463056 04-08 106
094 06-14 138078 06-09 431
070 05-09 258098 08-13 296
074 06-09 298096 07-13 271
074 06-10 301093 07-12 268
071 05-09 211079 05-12 117096 07-13 241
073 04-12 74077 05-13 71086 07-11 424
Fact
ors
Moore et al JCO 2007
ADVANCED DISEASE
Events
Tarceva () n=282
Placebo () n=280
Any Grade 34 Any Grade 34Rash 72 6 29 1Diarrhoea 56 6 41 2Infection 43 17 34 16Stomatitis 23 lt1 14 0Pneumonitis 2 2 1 lt1Fatigue 89 15 86 15
PA3 studyPA3 study Adverse eventsAdverse events
Moore et al JCO 2007
ADVANCED DISEASE
AccetableAccetable standard standard systemicsystemic treatmenttreatment options 2009options 2009
bullbull GEM GEM alonealonebullbull GEMGEM--erlotiniberlotinib
ndashndash registredregistred for for metastaticmetastatic PC PC onlyonly mOSmOS + 12 + 12 daysdays somesome additionaladditional toxicitytoxicity
bullbull GEMGEM--CAP CAP mOSmOS + 1 + 1 monthmonth onlyonly significantsignificant in in metameta--analysisanalysis
bullbull GEMGEM--platinumplatinum ndashndash doubtfuldoubtful effecteffect -- nownow not not significantsignificant in in metameta--
analysisanalysis significantsignificant toxicitytoxicity
ADVANCED DISEASE
SUPPORTIVE CARESUPPORTIVE CARE
Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer
SUPPORTIVE CARE
GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)
enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009
Baggrund
VTE forekommer hos ca 10 af patienter med PC
Formaringl
Undersoslashge effekt af LMWH (Klexane) i kombination med
kemoterapi mht frekvens af VTE og mOS
Inklusion
Avanceret PC ikke tidligere kemoterapi
Karnofsky
PS gt 60
Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor
2 aringr
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al ASCO 2009
Antal af VTE 15152 i observation ndash 2160 i LMWH
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al
Konklusion
LMWH er effektiv og sikker behandling til forebyggelse af
VTE hos patienter med pancreascancer
Endelige resultater paring
mOS og mTTP
afventes
SUPPORTIVE CARE
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
ESPACESPAC‐‐33ESPAC‐3 A multicenter international open‐label randomized controlled
phase
III trial
of adjuvant
5‐fluorouracilfolinic
acid
(5‐FUFA) versus gemcitabine
(GEM) in patients with
resected
pancreatic
ductal
adenocarcinoma
Neoptolemos
et al
ASCO 2009
Gemcitabin
1 gang om ugen i
6 cyklusN=537
5FU+ folinsyre
i 5 dage hver
28 dag i 6 cyklusN=551
1088 pt
RESECTABLE DISEASE
3 arm BSC lukket pr3 arm BSC lukket praeligaeligmaturt grundet signifikant effekt af Gem maturt grundet signifikant effekt af Gem vsvs BSCBSCR0R1 R0R1 resektionresektion lt 8 uger efter operationlt 8 uger efter operation
ESPACESPAC‐‐33ESPAC‐3 A multicenter international open‐label randomized controlled
phase
III trial
of adjuvant
5‐fluorouracilfolinic
acid
(5‐FUFA) versus gemcitabine
(GEM) in patients with
resected
pancreatic
ductal
adenocarcinoma
Neoptolemos
et al
RESECTABLE DISEASE
News 2009 News 2009 adjuvantadjuvant treatmenttreatment
bullbull Gem Gem ogog 5FU 5FU erer ligelige effektiveeffektive men Gem men Gem erer mindstmindst toksisktoksisk
bullbull GemCapGemCap
vs Gem er i fase III (ESPACvs Gem er i fase III (ESPAC‐‐4)4)
RESECTABLE DISEASE
LOCALLY ADVANCED DISEASELOCALLY ADVANCED DISEASE
OptionsOptions
bullbull ChemotherapyChemotherapyndashndash GemGemndashndash Gem in combinationsGem in combinations
bullbull ChemoradiotherapyChemoradiotherapy
LOCALLY ADVANCED DISEASE
Overall survival on GemOverall survival on Gem
Storinolo et al Cancer 1998
LOCALLY ADVANCED DISEASE
ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT
LOCALLY ADVANCED DISEASE
LOCALLY ADVANCED DISEASE
ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT
LOCALLY ADVANCED DISEASE
LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT
LOCALLY ADVANCED DISEASE
LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT
LOCALLY ADVANCED DISEASE
Wilkowski
et al Final analysis
of a multicenter randomized
phase
II trial
comparing
three
different
chemoradiotherapy
regimens
in the treatment
of patients with
locally
advanced nonmetastatic
pancreatic
cancer ASCO 2009
Cis‐gemDag 1 8 22 29
Og cis‐gem
efter KRT
Kontinuerlig 5FU
Cis‐gemDag 18 22 2995 pt
ndashndash 3 forskellige kemo3 forskellige kemo‐‐regimer med regimer med konkomittantkonkomittant
strstraringaringlebehandling lebehandling aacuteaacute 50GY25fr 50GY25fr
LOCALLY ADVANCED DISEASE
Final analysis
of a multicenter randomized
phase
II trial
comparing
three
different
chemoradiotherapy
regimens
in the
treatment
of patients with
locally
advanced nonmetastatic
pancreatic
cancer Ralf
Wilkowski
bull 18 patienter blev opereret Fordeling ukendtbull Hoslashjere frekvens af grad 34 haeligmotologiske
bivirkninger i GC armene
bull Ingen forskel mellem 5FU og GemCis
PFSPFS((mdrmdr))
OSOS((mdrmdr))
HHaeligaeligmtoxmtox DiarreDiarre
RKTRKT--5FU5FU 44 9696 ++RKTRKT--GCGC 5656 9393 ++RKTRKT--GC + GCGC + GC 66 7373 ++
LOCALLY ADVANCED DISEASE
KonklusionerKonklusioner
bullbull StadigStadig ikkeikke afklaretafklaret omom kemokemo--radioterapiradioterapi forlforlaeligaeligngernger overlevelsenoverlevelsen i i forholdforhold tiltil kemoterapikemoterapi alenealene
bullbull IkkeIkke afklaretafklaret hvilkenhvilken kemoterapikemoterapi derder erer bedstbedst sammensammen med med radioterapiradioterapi
bullbull KemoKemo--radioterapiradioterapi kankan i i udvalgteudvalgte tilftilfaeligaeligldelde medfmedfoslashoslashrere konverteringkonvertering afaf sygdomsygdom frafra ikkeikke--resektabelresektabel tiltil resektabelresektabel men men detdet kankan kemoterapikemoterapi alenealene ogsogsaringaring
LOCALLY ADVANCED DISEASE
Herrmann 2008
LOCALLY ADVANCED DISEASE
ADVANCED DISEASEADVANCED DISEASE
AdvancedAdvanced diseasedisease
bullbull Median Median survivalsurvival untreateduntreated 33--4 4 monthsmonthsbullbull PrimaryPrimary goalsgoals of of treatmenttreatment
ndashndash Prolongation of Prolongation of survivalsurvivalndashndash ImprovementImprovement in in QoLQoL
ADVANCED DISEASE
GemcitabineGemcitabine vs 5vs 5--FUFU
Burris H et al J Clin Oncol 1997152403-2413
Gemcitabine 5-FU P
Clinical benefit response 24 5 0002 Median survival (months) 57 44 0002 Time to progression (months) 21 09 0001 6-month survival 46 31 1-year survival 18 2 Partial response 54 0 Stable disease 393 19 Composite of measurements of pain (analgesic consumption and pain intensity) Karnofsky
performance status and weight
ADVANCED DISEASE
SurvivalSurvival of of GemGem--treatedtreated patients patients accordingaccording to performance statusto performance status
Storinolo et al Cancer 1998
ADVANCED DISEASE
Combination chemotherapyCombination chemotherapy GemGem--CapCap
JCO october 2009
ADVANCED DISEASE
CunninghamCunningham et al GEMet al GEM--CAPCAP
Hazard ratio 080 95 CI 065ndash098Log-rank p=0026
Eur J Cancer Suppl 2005
Interim analysis 2005Final analysis 2009
ADVANCED DISEASE
MetaMeta--analysisanalysis of GEMof GEM--CAPCAP
Cunningham et al JCO 2009
ADVANCED DISEASE
Gem vs Gem vs GemGem‐‐platinumplatinumDi Miao A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
ASCO 2009
Gemcitabin
som kontrol +
cisplatin
ugentlig 25mgm2N=201
Gemcitabin
ugentlig i 7 uger
2 ugers pause og dag 18 15 i
4 ugers cyklusN=199
400 pt
ADVANCED DISEASE
GemGem GemCisGemCis
OSOS11‐‐year year survivalsurvivalPFSPFS
AnAnaeligaeligmimiTrombocytopeniTrombocytopeni
83 mdr 83 mdr 340 340 39 mdr 39 mdr
39392929
72 mdr 72 mdr 307 307 38 mdr38 mdr
50505757
A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma
The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
Di Miao
bull Alle endepunkter insignifikantebull Subgruppeanalyse
af PS 0 Signifikant negativ effekt
bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant
efter inklusion af dette studium
ADVANCED DISEASE
CombinationCombination chemotherapychemotherapy and and effecteffect accordingaccording to to performance statusperformance status
Heinemann et al BMC Cancer 2008
ADVANCED DISEASE
PA3 study GemPA3 study Gem--erlotiniberlotinib Overall survivalOverall survival
10090807060504030201
0
Surv
ival
pro
babi
lity
0 6 12 18 24Survival (months)
Tarcevatrade gemcitabine
(n=285)
Placebo gemcitabine
(n=284)
Median survival (months) 637 591
1-year survival 24 17
HR=079 (95 CI 066-095) P=0011 (adjusted for PS and extent of disease at randomization)
TarcevaTM + gemcitabinePlacebo + gemcitabine
Moore et al JCO 2007
ADVANCED DISEASE
PA3 studyPA3 study Hazard ratios for survivalHazard ratios for survival
HR 95 CI n
Tarcevaplacebo
Performance status 0-1Performance status 2
Locally advancedDistant metastasis
Pain 20 Pain gt20
MaleFemale
Age lt65Age 65
United StatesCanada
Rest of World
HER1EGFR positiveHER1EGFR negative
HER1EGFR unknown
1
082 07-10 569
087 07-11 463056 04-08 106
094 06-14 138078 06-09 431
070 05-09 258098 08-13 296
074 06-09 298096 07-13 271
074 06-10 301093 07-12 268
071 05-09 211079 05-12 117096 07-13 241
073 04-12 74077 05-13 71086 07-11 424
Fact
ors
Moore et al JCO 2007
ADVANCED DISEASE
Events
Tarceva () n=282
Placebo () n=280
Any Grade 34 Any Grade 34Rash 72 6 29 1Diarrhoea 56 6 41 2Infection 43 17 34 16Stomatitis 23 lt1 14 0Pneumonitis 2 2 1 lt1Fatigue 89 15 86 15
PA3 studyPA3 study Adverse eventsAdverse events
Moore et al JCO 2007
ADVANCED DISEASE
AccetableAccetable standard standard systemicsystemic treatmenttreatment options 2009options 2009
bullbull GEM GEM alonealonebullbull GEMGEM--erlotiniberlotinib
ndashndash registredregistred for for metastaticmetastatic PC PC onlyonly mOSmOS + 12 + 12 daysdays somesome additionaladditional toxicitytoxicity
bullbull GEMGEM--CAP CAP mOSmOS + 1 + 1 monthmonth onlyonly significantsignificant in in metameta--analysisanalysis
bullbull GEMGEM--platinumplatinum ndashndash doubtfuldoubtful effecteffect -- nownow not not significantsignificant in in metameta--
analysisanalysis significantsignificant toxicitytoxicity
ADVANCED DISEASE
SUPPORTIVE CARESUPPORTIVE CARE
Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer
SUPPORTIVE CARE
GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)
enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009
Baggrund
VTE forekommer hos ca 10 af patienter med PC
Formaringl
Undersoslashge effekt af LMWH (Klexane) i kombination med
kemoterapi mht frekvens af VTE og mOS
Inklusion
Avanceret PC ikke tidligere kemoterapi
Karnofsky
PS gt 60
Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor
2 aringr
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al ASCO 2009
Antal af VTE 15152 i observation ndash 2160 i LMWH
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al
Konklusion
LMWH er effektiv og sikker behandling til forebyggelse af
VTE hos patienter med pancreascancer
Endelige resultater paring
mOS og mTTP
afventes
SUPPORTIVE CARE
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
ESPACESPAC‐‐33ESPAC‐3 A multicenter international open‐label randomized controlled
phase
III trial
of adjuvant
5‐fluorouracilfolinic
acid
(5‐FUFA) versus gemcitabine
(GEM) in patients with
resected
pancreatic
ductal
adenocarcinoma
Neoptolemos
et al
RESECTABLE DISEASE
News 2009 News 2009 adjuvantadjuvant treatmenttreatment
bullbull Gem Gem ogog 5FU 5FU erer ligelige effektiveeffektive men Gem men Gem erer mindstmindst toksisktoksisk
bullbull GemCapGemCap
vs Gem er i fase III (ESPACvs Gem er i fase III (ESPAC‐‐4)4)
RESECTABLE DISEASE
LOCALLY ADVANCED DISEASELOCALLY ADVANCED DISEASE
OptionsOptions
bullbull ChemotherapyChemotherapyndashndash GemGemndashndash Gem in combinationsGem in combinations
bullbull ChemoradiotherapyChemoradiotherapy
LOCALLY ADVANCED DISEASE
Overall survival on GemOverall survival on Gem
Storinolo et al Cancer 1998
LOCALLY ADVANCED DISEASE
ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT
LOCALLY ADVANCED DISEASE
LOCALLY ADVANCED DISEASE
ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT
LOCALLY ADVANCED DISEASE
LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT
LOCALLY ADVANCED DISEASE
LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT
LOCALLY ADVANCED DISEASE
Wilkowski
et al Final analysis
of a multicenter randomized
phase
II trial
comparing
three
different
chemoradiotherapy
regimens
in the treatment
of patients with
locally
advanced nonmetastatic
pancreatic
cancer ASCO 2009
Cis‐gemDag 1 8 22 29
Og cis‐gem
efter KRT
Kontinuerlig 5FU
Cis‐gemDag 18 22 2995 pt
ndashndash 3 forskellige kemo3 forskellige kemo‐‐regimer med regimer med konkomittantkonkomittant
strstraringaringlebehandling lebehandling aacuteaacute 50GY25fr 50GY25fr
LOCALLY ADVANCED DISEASE
Final analysis
of a multicenter randomized
phase
II trial
comparing
three
different
chemoradiotherapy
regimens
in the
treatment
of patients with
locally
advanced nonmetastatic
pancreatic
cancer Ralf
Wilkowski
bull 18 patienter blev opereret Fordeling ukendtbull Hoslashjere frekvens af grad 34 haeligmotologiske
bivirkninger i GC armene
bull Ingen forskel mellem 5FU og GemCis
PFSPFS((mdrmdr))
OSOS((mdrmdr))
HHaeligaeligmtoxmtox DiarreDiarre
RKTRKT--5FU5FU 44 9696 ++RKTRKT--GCGC 5656 9393 ++RKTRKT--GC + GCGC + GC 66 7373 ++
LOCALLY ADVANCED DISEASE
KonklusionerKonklusioner
bullbull StadigStadig ikkeikke afklaretafklaret omom kemokemo--radioterapiradioterapi forlforlaeligaeligngernger overlevelsenoverlevelsen i i forholdforhold tiltil kemoterapikemoterapi alenealene
bullbull IkkeIkke afklaretafklaret hvilkenhvilken kemoterapikemoterapi derder erer bedstbedst sammensammen med med radioterapiradioterapi
bullbull KemoKemo--radioterapiradioterapi kankan i i udvalgteudvalgte tilftilfaeligaeligldelde medfmedfoslashoslashrere konverteringkonvertering afaf sygdomsygdom frafra ikkeikke--resektabelresektabel tiltil resektabelresektabel men men detdet kankan kemoterapikemoterapi alenealene ogsogsaringaring
LOCALLY ADVANCED DISEASE
Herrmann 2008
LOCALLY ADVANCED DISEASE
ADVANCED DISEASEADVANCED DISEASE
AdvancedAdvanced diseasedisease
bullbull Median Median survivalsurvival untreateduntreated 33--4 4 monthsmonthsbullbull PrimaryPrimary goalsgoals of of treatmenttreatment
ndashndash Prolongation of Prolongation of survivalsurvivalndashndash ImprovementImprovement in in QoLQoL
ADVANCED DISEASE
GemcitabineGemcitabine vs 5vs 5--FUFU
Burris H et al J Clin Oncol 1997152403-2413
Gemcitabine 5-FU P
Clinical benefit response 24 5 0002 Median survival (months) 57 44 0002 Time to progression (months) 21 09 0001 6-month survival 46 31 1-year survival 18 2 Partial response 54 0 Stable disease 393 19 Composite of measurements of pain (analgesic consumption and pain intensity) Karnofsky
performance status and weight
ADVANCED DISEASE
SurvivalSurvival of of GemGem--treatedtreated patients patients accordingaccording to performance statusto performance status
Storinolo et al Cancer 1998
ADVANCED DISEASE
Combination chemotherapyCombination chemotherapy GemGem--CapCap
JCO october 2009
ADVANCED DISEASE
CunninghamCunningham et al GEMet al GEM--CAPCAP
Hazard ratio 080 95 CI 065ndash098Log-rank p=0026
Eur J Cancer Suppl 2005
Interim analysis 2005Final analysis 2009
ADVANCED DISEASE
MetaMeta--analysisanalysis of GEMof GEM--CAPCAP
Cunningham et al JCO 2009
ADVANCED DISEASE
Gem vs Gem vs GemGem‐‐platinumplatinumDi Miao A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
ASCO 2009
Gemcitabin
som kontrol +
cisplatin
ugentlig 25mgm2N=201
Gemcitabin
ugentlig i 7 uger
2 ugers pause og dag 18 15 i
4 ugers cyklusN=199
400 pt
ADVANCED DISEASE
GemGem GemCisGemCis
OSOS11‐‐year year survivalsurvivalPFSPFS
AnAnaeligaeligmimiTrombocytopeniTrombocytopeni
83 mdr 83 mdr 340 340 39 mdr 39 mdr
39392929
72 mdr 72 mdr 307 307 38 mdr38 mdr
50505757
A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma
The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
Di Miao
bull Alle endepunkter insignifikantebull Subgruppeanalyse
af PS 0 Signifikant negativ effekt
bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant
efter inklusion af dette studium
ADVANCED DISEASE
CombinationCombination chemotherapychemotherapy and and effecteffect accordingaccording to to performance statusperformance status
Heinemann et al BMC Cancer 2008
ADVANCED DISEASE
PA3 study GemPA3 study Gem--erlotiniberlotinib Overall survivalOverall survival
10090807060504030201
0
Surv
ival
pro
babi
lity
0 6 12 18 24Survival (months)
Tarcevatrade gemcitabine
(n=285)
Placebo gemcitabine
(n=284)
Median survival (months) 637 591
1-year survival 24 17
HR=079 (95 CI 066-095) P=0011 (adjusted for PS and extent of disease at randomization)
TarcevaTM + gemcitabinePlacebo + gemcitabine
Moore et al JCO 2007
ADVANCED DISEASE
PA3 studyPA3 study Hazard ratios for survivalHazard ratios for survival
HR 95 CI n
Tarcevaplacebo
Performance status 0-1Performance status 2
Locally advancedDistant metastasis
Pain 20 Pain gt20
MaleFemale
Age lt65Age 65
United StatesCanada
Rest of World
HER1EGFR positiveHER1EGFR negative
HER1EGFR unknown
1
082 07-10 569
087 07-11 463056 04-08 106
094 06-14 138078 06-09 431
070 05-09 258098 08-13 296
074 06-09 298096 07-13 271
074 06-10 301093 07-12 268
071 05-09 211079 05-12 117096 07-13 241
073 04-12 74077 05-13 71086 07-11 424
Fact
ors
Moore et al JCO 2007
ADVANCED DISEASE
Events
Tarceva () n=282
Placebo () n=280
Any Grade 34 Any Grade 34Rash 72 6 29 1Diarrhoea 56 6 41 2Infection 43 17 34 16Stomatitis 23 lt1 14 0Pneumonitis 2 2 1 lt1Fatigue 89 15 86 15
PA3 studyPA3 study Adverse eventsAdverse events
Moore et al JCO 2007
ADVANCED DISEASE
AccetableAccetable standard standard systemicsystemic treatmenttreatment options 2009options 2009
bullbull GEM GEM alonealonebullbull GEMGEM--erlotiniberlotinib
ndashndash registredregistred for for metastaticmetastatic PC PC onlyonly mOSmOS + 12 + 12 daysdays somesome additionaladditional toxicitytoxicity
bullbull GEMGEM--CAP CAP mOSmOS + 1 + 1 monthmonth onlyonly significantsignificant in in metameta--analysisanalysis
bullbull GEMGEM--platinumplatinum ndashndash doubtfuldoubtful effecteffect -- nownow not not significantsignificant in in metameta--
analysisanalysis significantsignificant toxicitytoxicity
ADVANCED DISEASE
SUPPORTIVE CARESUPPORTIVE CARE
Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer
SUPPORTIVE CARE
GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)
enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009
Baggrund
VTE forekommer hos ca 10 af patienter med PC
Formaringl
Undersoslashge effekt af LMWH (Klexane) i kombination med
kemoterapi mht frekvens af VTE og mOS
Inklusion
Avanceret PC ikke tidligere kemoterapi
Karnofsky
PS gt 60
Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor
2 aringr
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al ASCO 2009
Antal af VTE 15152 i observation ndash 2160 i LMWH
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al
Konklusion
LMWH er effektiv og sikker behandling til forebyggelse af
VTE hos patienter med pancreascancer
Endelige resultater paring
mOS og mTTP
afventes
SUPPORTIVE CARE
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
News 2009 News 2009 adjuvantadjuvant treatmenttreatment
bullbull Gem Gem ogog 5FU 5FU erer ligelige effektiveeffektive men Gem men Gem erer mindstmindst toksisktoksisk
bullbull GemCapGemCap
vs Gem er i fase III (ESPACvs Gem er i fase III (ESPAC‐‐4)4)
RESECTABLE DISEASE
LOCALLY ADVANCED DISEASELOCALLY ADVANCED DISEASE
OptionsOptions
bullbull ChemotherapyChemotherapyndashndash GemGemndashndash Gem in combinationsGem in combinations
bullbull ChemoradiotherapyChemoradiotherapy
LOCALLY ADVANCED DISEASE
Overall survival on GemOverall survival on Gem
Storinolo et al Cancer 1998
LOCALLY ADVANCED DISEASE
ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT
LOCALLY ADVANCED DISEASE
LOCALLY ADVANCED DISEASE
ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT
LOCALLY ADVANCED DISEASE
LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT
LOCALLY ADVANCED DISEASE
LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT
LOCALLY ADVANCED DISEASE
Wilkowski
et al Final analysis
of a multicenter randomized
phase
II trial
comparing
three
different
chemoradiotherapy
regimens
in the treatment
of patients with
locally
advanced nonmetastatic
pancreatic
cancer ASCO 2009
Cis‐gemDag 1 8 22 29
Og cis‐gem
efter KRT
Kontinuerlig 5FU
Cis‐gemDag 18 22 2995 pt
ndashndash 3 forskellige kemo3 forskellige kemo‐‐regimer med regimer med konkomittantkonkomittant
strstraringaringlebehandling lebehandling aacuteaacute 50GY25fr 50GY25fr
LOCALLY ADVANCED DISEASE
Final analysis
of a multicenter randomized
phase
II trial
comparing
three
different
chemoradiotherapy
regimens
in the
treatment
of patients with
locally
advanced nonmetastatic
pancreatic
cancer Ralf
Wilkowski
bull 18 patienter blev opereret Fordeling ukendtbull Hoslashjere frekvens af grad 34 haeligmotologiske
bivirkninger i GC armene
bull Ingen forskel mellem 5FU og GemCis
PFSPFS((mdrmdr))
OSOS((mdrmdr))
HHaeligaeligmtoxmtox DiarreDiarre
RKTRKT--5FU5FU 44 9696 ++RKTRKT--GCGC 5656 9393 ++RKTRKT--GC + GCGC + GC 66 7373 ++
LOCALLY ADVANCED DISEASE
KonklusionerKonklusioner
bullbull StadigStadig ikkeikke afklaretafklaret omom kemokemo--radioterapiradioterapi forlforlaeligaeligngernger overlevelsenoverlevelsen i i forholdforhold tiltil kemoterapikemoterapi alenealene
bullbull IkkeIkke afklaretafklaret hvilkenhvilken kemoterapikemoterapi derder erer bedstbedst sammensammen med med radioterapiradioterapi
bullbull KemoKemo--radioterapiradioterapi kankan i i udvalgteudvalgte tilftilfaeligaeligldelde medfmedfoslashoslashrere konverteringkonvertering afaf sygdomsygdom frafra ikkeikke--resektabelresektabel tiltil resektabelresektabel men men detdet kankan kemoterapikemoterapi alenealene ogsogsaringaring
LOCALLY ADVANCED DISEASE
Herrmann 2008
LOCALLY ADVANCED DISEASE
ADVANCED DISEASEADVANCED DISEASE
AdvancedAdvanced diseasedisease
bullbull Median Median survivalsurvival untreateduntreated 33--4 4 monthsmonthsbullbull PrimaryPrimary goalsgoals of of treatmenttreatment
ndashndash Prolongation of Prolongation of survivalsurvivalndashndash ImprovementImprovement in in QoLQoL
ADVANCED DISEASE
GemcitabineGemcitabine vs 5vs 5--FUFU
Burris H et al J Clin Oncol 1997152403-2413
Gemcitabine 5-FU P
Clinical benefit response 24 5 0002 Median survival (months) 57 44 0002 Time to progression (months) 21 09 0001 6-month survival 46 31 1-year survival 18 2 Partial response 54 0 Stable disease 393 19 Composite of measurements of pain (analgesic consumption and pain intensity) Karnofsky
performance status and weight
ADVANCED DISEASE
SurvivalSurvival of of GemGem--treatedtreated patients patients accordingaccording to performance statusto performance status
Storinolo et al Cancer 1998
ADVANCED DISEASE
Combination chemotherapyCombination chemotherapy GemGem--CapCap
JCO october 2009
ADVANCED DISEASE
CunninghamCunningham et al GEMet al GEM--CAPCAP
Hazard ratio 080 95 CI 065ndash098Log-rank p=0026
Eur J Cancer Suppl 2005
Interim analysis 2005Final analysis 2009
ADVANCED DISEASE
MetaMeta--analysisanalysis of GEMof GEM--CAPCAP
Cunningham et al JCO 2009
ADVANCED DISEASE
Gem vs Gem vs GemGem‐‐platinumplatinumDi Miao A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
ASCO 2009
Gemcitabin
som kontrol +
cisplatin
ugentlig 25mgm2N=201
Gemcitabin
ugentlig i 7 uger
2 ugers pause og dag 18 15 i
4 ugers cyklusN=199
400 pt
ADVANCED DISEASE
GemGem GemCisGemCis
OSOS11‐‐year year survivalsurvivalPFSPFS
AnAnaeligaeligmimiTrombocytopeniTrombocytopeni
83 mdr 83 mdr 340 340 39 mdr 39 mdr
39392929
72 mdr 72 mdr 307 307 38 mdr38 mdr
50505757
A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma
The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
Di Miao
bull Alle endepunkter insignifikantebull Subgruppeanalyse
af PS 0 Signifikant negativ effekt
bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant
efter inklusion af dette studium
ADVANCED DISEASE
CombinationCombination chemotherapychemotherapy and and effecteffect accordingaccording to to performance statusperformance status
Heinemann et al BMC Cancer 2008
ADVANCED DISEASE
PA3 study GemPA3 study Gem--erlotiniberlotinib Overall survivalOverall survival
10090807060504030201
0
Surv
ival
pro
babi
lity
0 6 12 18 24Survival (months)
Tarcevatrade gemcitabine
(n=285)
Placebo gemcitabine
(n=284)
Median survival (months) 637 591
1-year survival 24 17
HR=079 (95 CI 066-095) P=0011 (adjusted for PS and extent of disease at randomization)
TarcevaTM + gemcitabinePlacebo + gemcitabine
Moore et al JCO 2007
ADVANCED DISEASE
PA3 studyPA3 study Hazard ratios for survivalHazard ratios for survival
HR 95 CI n
Tarcevaplacebo
Performance status 0-1Performance status 2
Locally advancedDistant metastasis
Pain 20 Pain gt20
MaleFemale
Age lt65Age 65
United StatesCanada
Rest of World
HER1EGFR positiveHER1EGFR negative
HER1EGFR unknown
1
082 07-10 569
087 07-11 463056 04-08 106
094 06-14 138078 06-09 431
070 05-09 258098 08-13 296
074 06-09 298096 07-13 271
074 06-10 301093 07-12 268
071 05-09 211079 05-12 117096 07-13 241
073 04-12 74077 05-13 71086 07-11 424
Fact
ors
Moore et al JCO 2007
ADVANCED DISEASE
Events
Tarceva () n=282
Placebo () n=280
Any Grade 34 Any Grade 34Rash 72 6 29 1Diarrhoea 56 6 41 2Infection 43 17 34 16Stomatitis 23 lt1 14 0Pneumonitis 2 2 1 lt1Fatigue 89 15 86 15
PA3 studyPA3 study Adverse eventsAdverse events
Moore et al JCO 2007
ADVANCED DISEASE
AccetableAccetable standard standard systemicsystemic treatmenttreatment options 2009options 2009
bullbull GEM GEM alonealonebullbull GEMGEM--erlotiniberlotinib
ndashndash registredregistred for for metastaticmetastatic PC PC onlyonly mOSmOS + 12 + 12 daysdays somesome additionaladditional toxicitytoxicity
bullbull GEMGEM--CAP CAP mOSmOS + 1 + 1 monthmonth onlyonly significantsignificant in in metameta--analysisanalysis
bullbull GEMGEM--platinumplatinum ndashndash doubtfuldoubtful effecteffect -- nownow not not significantsignificant in in metameta--
analysisanalysis significantsignificant toxicitytoxicity
ADVANCED DISEASE
SUPPORTIVE CARESUPPORTIVE CARE
Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer
SUPPORTIVE CARE
GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)
enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009
Baggrund
VTE forekommer hos ca 10 af patienter med PC
Formaringl
Undersoslashge effekt af LMWH (Klexane) i kombination med
kemoterapi mht frekvens af VTE og mOS
Inklusion
Avanceret PC ikke tidligere kemoterapi
Karnofsky
PS gt 60
Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor
2 aringr
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al ASCO 2009
Antal af VTE 15152 i observation ndash 2160 i LMWH
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al
Konklusion
LMWH er effektiv og sikker behandling til forebyggelse af
VTE hos patienter med pancreascancer
Endelige resultater paring
mOS og mTTP
afventes
SUPPORTIVE CARE
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
LOCALLY ADVANCED DISEASELOCALLY ADVANCED DISEASE
OptionsOptions
bullbull ChemotherapyChemotherapyndashndash GemGemndashndash Gem in combinationsGem in combinations
bullbull ChemoradiotherapyChemoradiotherapy
LOCALLY ADVANCED DISEASE
Overall survival on GemOverall survival on Gem
Storinolo et al Cancer 1998
LOCALLY ADVANCED DISEASE
ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT
LOCALLY ADVANCED DISEASE
LOCALLY ADVANCED DISEASE
ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT
LOCALLY ADVANCED DISEASE
LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT
LOCALLY ADVANCED DISEASE
LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT
LOCALLY ADVANCED DISEASE
Wilkowski
et al Final analysis
of a multicenter randomized
phase
II trial
comparing
three
different
chemoradiotherapy
regimens
in the treatment
of patients with
locally
advanced nonmetastatic
pancreatic
cancer ASCO 2009
Cis‐gemDag 1 8 22 29
Og cis‐gem
efter KRT
Kontinuerlig 5FU
Cis‐gemDag 18 22 2995 pt
ndashndash 3 forskellige kemo3 forskellige kemo‐‐regimer med regimer med konkomittantkonkomittant
strstraringaringlebehandling lebehandling aacuteaacute 50GY25fr 50GY25fr
LOCALLY ADVANCED DISEASE
Final analysis
of a multicenter randomized
phase
II trial
comparing
three
different
chemoradiotherapy
regimens
in the
treatment
of patients with
locally
advanced nonmetastatic
pancreatic
cancer Ralf
Wilkowski
bull 18 patienter blev opereret Fordeling ukendtbull Hoslashjere frekvens af grad 34 haeligmotologiske
bivirkninger i GC armene
bull Ingen forskel mellem 5FU og GemCis
PFSPFS((mdrmdr))
OSOS((mdrmdr))
HHaeligaeligmtoxmtox DiarreDiarre
RKTRKT--5FU5FU 44 9696 ++RKTRKT--GCGC 5656 9393 ++RKTRKT--GC + GCGC + GC 66 7373 ++
LOCALLY ADVANCED DISEASE
KonklusionerKonklusioner
bullbull StadigStadig ikkeikke afklaretafklaret omom kemokemo--radioterapiradioterapi forlforlaeligaeligngernger overlevelsenoverlevelsen i i forholdforhold tiltil kemoterapikemoterapi alenealene
bullbull IkkeIkke afklaretafklaret hvilkenhvilken kemoterapikemoterapi derder erer bedstbedst sammensammen med med radioterapiradioterapi
bullbull KemoKemo--radioterapiradioterapi kankan i i udvalgteudvalgte tilftilfaeligaeligldelde medfmedfoslashoslashrere konverteringkonvertering afaf sygdomsygdom frafra ikkeikke--resektabelresektabel tiltil resektabelresektabel men men detdet kankan kemoterapikemoterapi alenealene ogsogsaringaring
LOCALLY ADVANCED DISEASE
Herrmann 2008
LOCALLY ADVANCED DISEASE
ADVANCED DISEASEADVANCED DISEASE
AdvancedAdvanced diseasedisease
bullbull Median Median survivalsurvival untreateduntreated 33--4 4 monthsmonthsbullbull PrimaryPrimary goalsgoals of of treatmenttreatment
ndashndash Prolongation of Prolongation of survivalsurvivalndashndash ImprovementImprovement in in QoLQoL
ADVANCED DISEASE
GemcitabineGemcitabine vs 5vs 5--FUFU
Burris H et al J Clin Oncol 1997152403-2413
Gemcitabine 5-FU P
Clinical benefit response 24 5 0002 Median survival (months) 57 44 0002 Time to progression (months) 21 09 0001 6-month survival 46 31 1-year survival 18 2 Partial response 54 0 Stable disease 393 19 Composite of measurements of pain (analgesic consumption and pain intensity) Karnofsky
performance status and weight
ADVANCED DISEASE
SurvivalSurvival of of GemGem--treatedtreated patients patients accordingaccording to performance statusto performance status
Storinolo et al Cancer 1998
ADVANCED DISEASE
Combination chemotherapyCombination chemotherapy GemGem--CapCap
JCO october 2009
ADVANCED DISEASE
CunninghamCunningham et al GEMet al GEM--CAPCAP
Hazard ratio 080 95 CI 065ndash098Log-rank p=0026
Eur J Cancer Suppl 2005
Interim analysis 2005Final analysis 2009
ADVANCED DISEASE
MetaMeta--analysisanalysis of GEMof GEM--CAPCAP
Cunningham et al JCO 2009
ADVANCED DISEASE
Gem vs Gem vs GemGem‐‐platinumplatinumDi Miao A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
ASCO 2009
Gemcitabin
som kontrol +
cisplatin
ugentlig 25mgm2N=201
Gemcitabin
ugentlig i 7 uger
2 ugers pause og dag 18 15 i
4 ugers cyklusN=199
400 pt
ADVANCED DISEASE
GemGem GemCisGemCis
OSOS11‐‐year year survivalsurvivalPFSPFS
AnAnaeligaeligmimiTrombocytopeniTrombocytopeni
83 mdr 83 mdr 340 340 39 mdr 39 mdr
39392929
72 mdr 72 mdr 307 307 38 mdr38 mdr
50505757
A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma
The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
Di Miao
bull Alle endepunkter insignifikantebull Subgruppeanalyse
af PS 0 Signifikant negativ effekt
bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant
efter inklusion af dette studium
ADVANCED DISEASE
CombinationCombination chemotherapychemotherapy and and effecteffect accordingaccording to to performance statusperformance status
Heinemann et al BMC Cancer 2008
ADVANCED DISEASE
PA3 study GemPA3 study Gem--erlotiniberlotinib Overall survivalOverall survival
10090807060504030201
0
Surv
ival
pro
babi
lity
0 6 12 18 24Survival (months)
Tarcevatrade gemcitabine
(n=285)
Placebo gemcitabine
(n=284)
Median survival (months) 637 591
1-year survival 24 17
HR=079 (95 CI 066-095) P=0011 (adjusted for PS and extent of disease at randomization)
TarcevaTM + gemcitabinePlacebo + gemcitabine
Moore et al JCO 2007
ADVANCED DISEASE
PA3 studyPA3 study Hazard ratios for survivalHazard ratios for survival
HR 95 CI n
Tarcevaplacebo
Performance status 0-1Performance status 2
Locally advancedDistant metastasis
Pain 20 Pain gt20
MaleFemale
Age lt65Age 65
United StatesCanada
Rest of World
HER1EGFR positiveHER1EGFR negative
HER1EGFR unknown
1
082 07-10 569
087 07-11 463056 04-08 106
094 06-14 138078 06-09 431
070 05-09 258098 08-13 296
074 06-09 298096 07-13 271
074 06-10 301093 07-12 268
071 05-09 211079 05-12 117096 07-13 241
073 04-12 74077 05-13 71086 07-11 424
Fact
ors
Moore et al JCO 2007
ADVANCED DISEASE
Events
Tarceva () n=282
Placebo () n=280
Any Grade 34 Any Grade 34Rash 72 6 29 1Diarrhoea 56 6 41 2Infection 43 17 34 16Stomatitis 23 lt1 14 0Pneumonitis 2 2 1 lt1Fatigue 89 15 86 15
PA3 studyPA3 study Adverse eventsAdverse events
Moore et al JCO 2007
ADVANCED DISEASE
AccetableAccetable standard standard systemicsystemic treatmenttreatment options 2009options 2009
bullbull GEM GEM alonealonebullbull GEMGEM--erlotiniberlotinib
ndashndash registredregistred for for metastaticmetastatic PC PC onlyonly mOSmOS + 12 + 12 daysdays somesome additionaladditional toxicitytoxicity
bullbull GEMGEM--CAP CAP mOSmOS + 1 + 1 monthmonth onlyonly significantsignificant in in metameta--analysisanalysis
bullbull GEMGEM--platinumplatinum ndashndash doubtfuldoubtful effecteffect -- nownow not not significantsignificant in in metameta--
analysisanalysis significantsignificant toxicitytoxicity
ADVANCED DISEASE
SUPPORTIVE CARESUPPORTIVE CARE
Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer
SUPPORTIVE CARE
GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)
enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009
Baggrund
VTE forekommer hos ca 10 af patienter med PC
Formaringl
Undersoslashge effekt af LMWH (Klexane) i kombination med
kemoterapi mht frekvens af VTE og mOS
Inklusion
Avanceret PC ikke tidligere kemoterapi
Karnofsky
PS gt 60
Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor
2 aringr
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al ASCO 2009
Antal af VTE 15152 i observation ndash 2160 i LMWH
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al
Konklusion
LMWH er effektiv og sikker behandling til forebyggelse af
VTE hos patienter med pancreascancer
Endelige resultater paring
mOS og mTTP
afventes
SUPPORTIVE CARE
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
OptionsOptions
bullbull ChemotherapyChemotherapyndashndash GemGemndashndash Gem in combinationsGem in combinations
bullbull ChemoradiotherapyChemoradiotherapy
LOCALLY ADVANCED DISEASE
Overall survival on GemOverall survival on Gem
Storinolo et al Cancer 1998
LOCALLY ADVANCED DISEASE
ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT
LOCALLY ADVANCED DISEASE
LOCALLY ADVANCED DISEASE
ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT
LOCALLY ADVANCED DISEASE
LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT
LOCALLY ADVANCED DISEASE
LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT
LOCALLY ADVANCED DISEASE
Wilkowski
et al Final analysis
of a multicenter randomized
phase
II trial
comparing
three
different
chemoradiotherapy
regimens
in the treatment
of patients with
locally
advanced nonmetastatic
pancreatic
cancer ASCO 2009
Cis‐gemDag 1 8 22 29
Og cis‐gem
efter KRT
Kontinuerlig 5FU
Cis‐gemDag 18 22 2995 pt
ndashndash 3 forskellige kemo3 forskellige kemo‐‐regimer med regimer med konkomittantkonkomittant
strstraringaringlebehandling lebehandling aacuteaacute 50GY25fr 50GY25fr
LOCALLY ADVANCED DISEASE
Final analysis
of a multicenter randomized
phase
II trial
comparing
three
different
chemoradiotherapy
regimens
in the
treatment
of patients with
locally
advanced nonmetastatic
pancreatic
cancer Ralf
Wilkowski
bull 18 patienter blev opereret Fordeling ukendtbull Hoslashjere frekvens af grad 34 haeligmotologiske
bivirkninger i GC armene
bull Ingen forskel mellem 5FU og GemCis
PFSPFS((mdrmdr))
OSOS((mdrmdr))
HHaeligaeligmtoxmtox DiarreDiarre
RKTRKT--5FU5FU 44 9696 ++RKTRKT--GCGC 5656 9393 ++RKTRKT--GC + GCGC + GC 66 7373 ++
LOCALLY ADVANCED DISEASE
KonklusionerKonklusioner
bullbull StadigStadig ikkeikke afklaretafklaret omom kemokemo--radioterapiradioterapi forlforlaeligaeligngernger overlevelsenoverlevelsen i i forholdforhold tiltil kemoterapikemoterapi alenealene
bullbull IkkeIkke afklaretafklaret hvilkenhvilken kemoterapikemoterapi derder erer bedstbedst sammensammen med med radioterapiradioterapi
bullbull KemoKemo--radioterapiradioterapi kankan i i udvalgteudvalgte tilftilfaeligaeligldelde medfmedfoslashoslashrere konverteringkonvertering afaf sygdomsygdom frafra ikkeikke--resektabelresektabel tiltil resektabelresektabel men men detdet kankan kemoterapikemoterapi alenealene ogsogsaringaring
LOCALLY ADVANCED DISEASE
Herrmann 2008
LOCALLY ADVANCED DISEASE
ADVANCED DISEASEADVANCED DISEASE
AdvancedAdvanced diseasedisease
bullbull Median Median survivalsurvival untreateduntreated 33--4 4 monthsmonthsbullbull PrimaryPrimary goalsgoals of of treatmenttreatment
ndashndash Prolongation of Prolongation of survivalsurvivalndashndash ImprovementImprovement in in QoLQoL
ADVANCED DISEASE
GemcitabineGemcitabine vs 5vs 5--FUFU
Burris H et al J Clin Oncol 1997152403-2413
Gemcitabine 5-FU P
Clinical benefit response 24 5 0002 Median survival (months) 57 44 0002 Time to progression (months) 21 09 0001 6-month survival 46 31 1-year survival 18 2 Partial response 54 0 Stable disease 393 19 Composite of measurements of pain (analgesic consumption and pain intensity) Karnofsky
performance status and weight
ADVANCED DISEASE
SurvivalSurvival of of GemGem--treatedtreated patients patients accordingaccording to performance statusto performance status
Storinolo et al Cancer 1998
ADVANCED DISEASE
Combination chemotherapyCombination chemotherapy GemGem--CapCap
JCO october 2009
ADVANCED DISEASE
CunninghamCunningham et al GEMet al GEM--CAPCAP
Hazard ratio 080 95 CI 065ndash098Log-rank p=0026
Eur J Cancer Suppl 2005
Interim analysis 2005Final analysis 2009
ADVANCED DISEASE
MetaMeta--analysisanalysis of GEMof GEM--CAPCAP
Cunningham et al JCO 2009
ADVANCED DISEASE
Gem vs Gem vs GemGem‐‐platinumplatinumDi Miao A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
ASCO 2009
Gemcitabin
som kontrol +
cisplatin
ugentlig 25mgm2N=201
Gemcitabin
ugentlig i 7 uger
2 ugers pause og dag 18 15 i
4 ugers cyklusN=199
400 pt
ADVANCED DISEASE
GemGem GemCisGemCis
OSOS11‐‐year year survivalsurvivalPFSPFS
AnAnaeligaeligmimiTrombocytopeniTrombocytopeni
83 mdr 83 mdr 340 340 39 mdr 39 mdr
39392929
72 mdr 72 mdr 307 307 38 mdr38 mdr
50505757
A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma
The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
Di Miao
bull Alle endepunkter insignifikantebull Subgruppeanalyse
af PS 0 Signifikant negativ effekt
bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant
efter inklusion af dette studium
ADVANCED DISEASE
CombinationCombination chemotherapychemotherapy and and effecteffect accordingaccording to to performance statusperformance status
Heinemann et al BMC Cancer 2008
ADVANCED DISEASE
PA3 study GemPA3 study Gem--erlotiniberlotinib Overall survivalOverall survival
10090807060504030201
0
Surv
ival
pro
babi
lity
0 6 12 18 24Survival (months)
Tarcevatrade gemcitabine
(n=285)
Placebo gemcitabine
(n=284)
Median survival (months) 637 591
1-year survival 24 17
HR=079 (95 CI 066-095) P=0011 (adjusted for PS and extent of disease at randomization)
TarcevaTM + gemcitabinePlacebo + gemcitabine
Moore et al JCO 2007
ADVANCED DISEASE
PA3 studyPA3 study Hazard ratios for survivalHazard ratios for survival
HR 95 CI n
Tarcevaplacebo
Performance status 0-1Performance status 2
Locally advancedDistant metastasis
Pain 20 Pain gt20
MaleFemale
Age lt65Age 65
United StatesCanada
Rest of World
HER1EGFR positiveHER1EGFR negative
HER1EGFR unknown
1
082 07-10 569
087 07-11 463056 04-08 106
094 06-14 138078 06-09 431
070 05-09 258098 08-13 296
074 06-09 298096 07-13 271
074 06-10 301093 07-12 268
071 05-09 211079 05-12 117096 07-13 241
073 04-12 74077 05-13 71086 07-11 424
Fact
ors
Moore et al JCO 2007
ADVANCED DISEASE
Events
Tarceva () n=282
Placebo () n=280
Any Grade 34 Any Grade 34Rash 72 6 29 1Diarrhoea 56 6 41 2Infection 43 17 34 16Stomatitis 23 lt1 14 0Pneumonitis 2 2 1 lt1Fatigue 89 15 86 15
PA3 studyPA3 study Adverse eventsAdverse events
Moore et al JCO 2007
ADVANCED DISEASE
AccetableAccetable standard standard systemicsystemic treatmenttreatment options 2009options 2009
bullbull GEM GEM alonealonebullbull GEMGEM--erlotiniberlotinib
ndashndash registredregistred for for metastaticmetastatic PC PC onlyonly mOSmOS + 12 + 12 daysdays somesome additionaladditional toxicitytoxicity
bullbull GEMGEM--CAP CAP mOSmOS + 1 + 1 monthmonth onlyonly significantsignificant in in metameta--analysisanalysis
bullbull GEMGEM--platinumplatinum ndashndash doubtfuldoubtful effecteffect -- nownow not not significantsignificant in in metameta--
analysisanalysis significantsignificant toxicitytoxicity
ADVANCED DISEASE
SUPPORTIVE CARESUPPORTIVE CARE
Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer
SUPPORTIVE CARE
GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)
enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009
Baggrund
VTE forekommer hos ca 10 af patienter med PC
Formaringl
Undersoslashge effekt af LMWH (Klexane) i kombination med
kemoterapi mht frekvens af VTE og mOS
Inklusion
Avanceret PC ikke tidligere kemoterapi
Karnofsky
PS gt 60
Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor
2 aringr
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al ASCO 2009
Antal af VTE 15152 i observation ndash 2160 i LMWH
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al
Konklusion
LMWH er effektiv og sikker behandling til forebyggelse af
VTE hos patienter med pancreascancer
Endelige resultater paring
mOS og mTTP
afventes
SUPPORTIVE CARE
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
Overall survival on GemOverall survival on Gem
Storinolo et al Cancer 1998
LOCALLY ADVANCED DISEASE
ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT
LOCALLY ADVANCED DISEASE
LOCALLY ADVANCED DISEASE
ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT
LOCALLY ADVANCED DISEASE
LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT
LOCALLY ADVANCED DISEASE
LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT
LOCALLY ADVANCED DISEASE
Wilkowski
et al Final analysis
of a multicenter randomized
phase
II trial
comparing
three
different
chemoradiotherapy
regimens
in the treatment
of patients with
locally
advanced nonmetastatic
pancreatic
cancer ASCO 2009
Cis‐gemDag 1 8 22 29
Og cis‐gem
efter KRT
Kontinuerlig 5FU
Cis‐gemDag 18 22 2995 pt
ndashndash 3 forskellige kemo3 forskellige kemo‐‐regimer med regimer med konkomittantkonkomittant
strstraringaringlebehandling lebehandling aacuteaacute 50GY25fr 50GY25fr
LOCALLY ADVANCED DISEASE
Final analysis
of a multicenter randomized
phase
II trial
comparing
three
different
chemoradiotherapy
regimens
in the
treatment
of patients with
locally
advanced nonmetastatic
pancreatic
cancer Ralf
Wilkowski
bull 18 patienter blev opereret Fordeling ukendtbull Hoslashjere frekvens af grad 34 haeligmotologiske
bivirkninger i GC armene
bull Ingen forskel mellem 5FU og GemCis
PFSPFS((mdrmdr))
OSOS((mdrmdr))
HHaeligaeligmtoxmtox DiarreDiarre
RKTRKT--5FU5FU 44 9696 ++RKTRKT--GCGC 5656 9393 ++RKTRKT--GC + GCGC + GC 66 7373 ++
LOCALLY ADVANCED DISEASE
KonklusionerKonklusioner
bullbull StadigStadig ikkeikke afklaretafklaret omom kemokemo--radioterapiradioterapi forlforlaeligaeligngernger overlevelsenoverlevelsen i i forholdforhold tiltil kemoterapikemoterapi alenealene
bullbull IkkeIkke afklaretafklaret hvilkenhvilken kemoterapikemoterapi derder erer bedstbedst sammensammen med med radioterapiradioterapi
bullbull KemoKemo--radioterapiradioterapi kankan i i udvalgteudvalgte tilftilfaeligaeligldelde medfmedfoslashoslashrere konverteringkonvertering afaf sygdomsygdom frafra ikkeikke--resektabelresektabel tiltil resektabelresektabel men men detdet kankan kemoterapikemoterapi alenealene ogsogsaringaring
LOCALLY ADVANCED DISEASE
Herrmann 2008
LOCALLY ADVANCED DISEASE
ADVANCED DISEASEADVANCED DISEASE
AdvancedAdvanced diseasedisease
bullbull Median Median survivalsurvival untreateduntreated 33--4 4 monthsmonthsbullbull PrimaryPrimary goalsgoals of of treatmenttreatment
ndashndash Prolongation of Prolongation of survivalsurvivalndashndash ImprovementImprovement in in QoLQoL
ADVANCED DISEASE
GemcitabineGemcitabine vs 5vs 5--FUFU
Burris H et al J Clin Oncol 1997152403-2413
Gemcitabine 5-FU P
Clinical benefit response 24 5 0002 Median survival (months) 57 44 0002 Time to progression (months) 21 09 0001 6-month survival 46 31 1-year survival 18 2 Partial response 54 0 Stable disease 393 19 Composite of measurements of pain (analgesic consumption and pain intensity) Karnofsky
performance status and weight
ADVANCED DISEASE
SurvivalSurvival of of GemGem--treatedtreated patients patients accordingaccording to performance statusto performance status
Storinolo et al Cancer 1998
ADVANCED DISEASE
Combination chemotherapyCombination chemotherapy GemGem--CapCap
JCO october 2009
ADVANCED DISEASE
CunninghamCunningham et al GEMet al GEM--CAPCAP
Hazard ratio 080 95 CI 065ndash098Log-rank p=0026
Eur J Cancer Suppl 2005
Interim analysis 2005Final analysis 2009
ADVANCED DISEASE
MetaMeta--analysisanalysis of GEMof GEM--CAPCAP
Cunningham et al JCO 2009
ADVANCED DISEASE
Gem vs Gem vs GemGem‐‐platinumplatinumDi Miao A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
ASCO 2009
Gemcitabin
som kontrol +
cisplatin
ugentlig 25mgm2N=201
Gemcitabin
ugentlig i 7 uger
2 ugers pause og dag 18 15 i
4 ugers cyklusN=199
400 pt
ADVANCED DISEASE
GemGem GemCisGemCis
OSOS11‐‐year year survivalsurvivalPFSPFS
AnAnaeligaeligmimiTrombocytopeniTrombocytopeni
83 mdr 83 mdr 340 340 39 mdr 39 mdr
39392929
72 mdr 72 mdr 307 307 38 mdr38 mdr
50505757
A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma
The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
Di Miao
bull Alle endepunkter insignifikantebull Subgruppeanalyse
af PS 0 Signifikant negativ effekt
bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant
efter inklusion af dette studium
ADVANCED DISEASE
CombinationCombination chemotherapychemotherapy and and effecteffect accordingaccording to to performance statusperformance status
Heinemann et al BMC Cancer 2008
ADVANCED DISEASE
PA3 study GemPA3 study Gem--erlotiniberlotinib Overall survivalOverall survival
10090807060504030201
0
Surv
ival
pro
babi
lity
0 6 12 18 24Survival (months)
Tarcevatrade gemcitabine
(n=285)
Placebo gemcitabine
(n=284)
Median survival (months) 637 591
1-year survival 24 17
HR=079 (95 CI 066-095) P=0011 (adjusted for PS and extent of disease at randomization)
TarcevaTM + gemcitabinePlacebo + gemcitabine
Moore et al JCO 2007
ADVANCED DISEASE
PA3 studyPA3 study Hazard ratios for survivalHazard ratios for survival
HR 95 CI n
Tarcevaplacebo
Performance status 0-1Performance status 2
Locally advancedDistant metastasis
Pain 20 Pain gt20
MaleFemale
Age lt65Age 65
United StatesCanada
Rest of World
HER1EGFR positiveHER1EGFR negative
HER1EGFR unknown
1
082 07-10 569
087 07-11 463056 04-08 106
094 06-14 138078 06-09 431
070 05-09 258098 08-13 296
074 06-09 298096 07-13 271
074 06-10 301093 07-12 268
071 05-09 211079 05-12 117096 07-13 241
073 04-12 74077 05-13 71086 07-11 424
Fact
ors
Moore et al JCO 2007
ADVANCED DISEASE
Events
Tarceva () n=282
Placebo () n=280
Any Grade 34 Any Grade 34Rash 72 6 29 1Diarrhoea 56 6 41 2Infection 43 17 34 16Stomatitis 23 lt1 14 0Pneumonitis 2 2 1 lt1Fatigue 89 15 86 15
PA3 studyPA3 study Adverse eventsAdverse events
Moore et al JCO 2007
ADVANCED DISEASE
AccetableAccetable standard standard systemicsystemic treatmenttreatment options 2009options 2009
bullbull GEM GEM alonealonebullbull GEMGEM--erlotiniberlotinib
ndashndash registredregistred for for metastaticmetastatic PC PC onlyonly mOSmOS + 12 + 12 daysdays somesome additionaladditional toxicitytoxicity
bullbull GEMGEM--CAP CAP mOSmOS + 1 + 1 monthmonth onlyonly significantsignificant in in metameta--analysisanalysis
bullbull GEMGEM--platinumplatinum ndashndash doubtfuldoubtful effecteffect -- nownow not not significantsignificant in in metameta--
analysisanalysis significantsignificant toxicitytoxicity
ADVANCED DISEASE
SUPPORTIVE CARESUPPORTIVE CARE
Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer
SUPPORTIVE CARE
GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)
enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009
Baggrund
VTE forekommer hos ca 10 af patienter med PC
Formaringl
Undersoslashge effekt af LMWH (Klexane) i kombination med
kemoterapi mht frekvens af VTE og mOS
Inklusion
Avanceret PC ikke tidligere kemoterapi
Karnofsky
PS gt 60
Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor
2 aringr
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al ASCO 2009
Antal af VTE 15152 i observation ndash 2160 i LMWH
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al
Konklusion
LMWH er effektiv og sikker behandling til forebyggelse af
VTE hos patienter med pancreascancer
Endelige resultater paring
mOS og mTTP
afventes
SUPPORTIVE CARE
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT
LOCALLY ADVANCED DISEASE
LOCALLY ADVANCED DISEASE
ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT
LOCALLY ADVANCED DISEASE
LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT
LOCALLY ADVANCED DISEASE
LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT
LOCALLY ADVANCED DISEASE
Wilkowski
et al Final analysis
of a multicenter randomized
phase
II trial
comparing
three
different
chemoradiotherapy
regimens
in the treatment
of patients with
locally
advanced nonmetastatic
pancreatic
cancer ASCO 2009
Cis‐gemDag 1 8 22 29
Og cis‐gem
efter KRT
Kontinuerlig 5FU
Cis‐gemDag 18 22 2995 pt
ndashndash 3 forskellige kemo3 forskellige kemo‐‐regimer med regimer med konkomittantkonkomittant
strstraringaringlebehandling lebehandling aacuteaacute 50GY25fr 50GY25fr
LOCALLY ADVANCED DISEASE
Final analysis
of a multicenter randomized
phase
II trial
comparing
three
different
chemoradiotherapy
regimens
in the
treatment
of patients with
locally
advanced nonmetastatic
pancreatic
cancer Ralf
Wilkowski
bull 18 patienter blev opereret Fordeling ukendtbull Hoslashjere frekvens af grad 34 haeligmotologiske
bivirkninger i GC armene
bull Ingen forskel mellem 5FU og GemCis
PFSPFS((mdrmdr))
OSOS((mdrmdr))
HHaeligaeligmtoxmtox DiarreDiarre
RKTRKT--5FU5FU 44 9696 ++RKTRKT--GCGC 5656 9393 ++RKTRKT--GC + GCGC + GC 66 7373 ++
LOCALLY ADVANCED DISEASE
KonklusionerKonklusioner
bullbull StadigStadig ikkeikke afklaretafklaret omom kemokemo--radioterapiradioterapi forlforlaeligaeligngernger overlevelsenoverlevelsen i i forholdforhold tiltil kemoterapikemoterapi alenealene
bullbull IkkeIkke afklaretafklaret hvilkenhvilken kemoterapikemoterapi derder erer bedstbedst sammensammen med med radioterapiradioterapi
bullbull KemoKemo--radioterapiradioterapi kankan i i udvalgteudvalgte tilftilfaeligaeligldelde medfmedfoslashoslashrere konverteringkonvertering afaf sygdomsygdom frafra ikkeikke--resektabelresektabel tiltil resektabelresektabel men men detdet kankan kemoterapikemoterapi alenealene ogsogsaringaring
LOCALLY ADVANCED DISEASE
Herrmann 2008
LOCALLY ADVANCED DISEASE
ADVANCED DISEASEADVANCED DISEASE
AdvancedAdvanced diseasedisease
bullbull Median Median survivalsurvival untreateduntreated 33--4 4 monthsmonthsbullbull PrimaryPrimary goalsgoals of of treatmenttreatment
ndashndash Prolongation of Prolongation of survivalsurvivalndashndash ImprovementImprovement in in QoLQoL
ADVANCED DISEASE
GemcitabineGemcitabine vs 5vs 5--FUFU
Burris H et al J Clin Oncol 1997152403-2413
Gemcitabine 5-FU P
Clinical benefit response 24 5 0002 Median survival (months) 57 44 0002 Time to progression (months) 21 09 0001 6-month survival 46 31 1-year survival 18 2 Partial response 54 0 Stable disease 393 19 Composite of measurements of pain (analgesic consumption and pain intensity) Karnofsky
performance status and weight
ADVANCED DISEASE
SurvivalSurvival of of GemGem--treatedtreated patients patients accordingaccording to performance statusto performance status
Storinolo et al Cancer 1998
ADVANCED DISEASE
Combination chemotherapyCombination chemotherapy GemGem--CapCap
JCO october 2009
ADVANCED DISEASE
CunninghamCunningham et al GEMet al GEM--CAPCAP
Hazard ratio 080 95 CI 065ndash098Log-rank p=0026
Eur J Cancer Suppl 2005
Interim analysis 2005Final analysis 2009
ADVANCED DISEASE
MetaMeta--analysisanalysis of GEMof GEM--CAPCAP
Cunningham et al JCO 2009
ADVANCED DISEASE
Gem vs Gem vs GemGem‐‐platinumplatinumDi Miao A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
ASCO 2009
Gemcitabin
som kontrol +
cisplatin
ugentlig 25mgm2N=201
Gemcitabin
ugentlig i 7 uger
2 ugers pause og dag 18 15 i
4 ugers cyklusN=199
400 pt
ADVANCED DISEASE
GemGem GemCisGemCis
OSOS11‐‐year year survivalsurvivalPFSPFS
AnAnaeligaeligmimiTrombocytopeniTrombocytopeni
83 mdr 83 mdr 340 340 39 mdr 39 mdr
39392929
72 mdr 72 mdr 307 307 38 mdr38 mdr
50505757
A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma
The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
Di Miao
bull Alle endepunkter insignifikantebull Subgruppeanalyse
af PS 0 Signifikant negativ effekt
bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant
efter inklusion af dette studium
ADVANCED DISEASE
CombinationCombination chemotherapychemotherapy and and effecteffect accordingaccording to to performance statusperformance status
Heinemann et al BMC Cancer 2008
ADVANCED DISEASE
PA3 study GemPA3 study Gem--erlotiniberlotinib Overall survivalOverall survival
10090807060504030201
0
Surv
ival
pro
babi
lity
0 6 12 18 24Survival (months)
Tarcevatrade gemcitabine
(n=285)
Placebo gemcitabine
(n=284)
Median survival (months) 637 591
1-year survival 24 17
HR=079 (95 CI 066-095) P=0011 (adjusted for PS and extent of disease at randomization)
TarcevaTM + gemcitabinePlacebo + gemcitabine
Moore et al JCO 2007
ADVANCED DISEASE
PA3 studyPA3 study Hazard ratios for survivalHazard ratios for survival
HR 95 CI n
Tarcevaplacebo
Performance status 0-1Performance status 2
Locally advancedDistant metastasis
Pain 20 Pain gt20
MaleFemale
Age lt65Age 65
United StatesCanada
Rest of World
HER1EGFR positiveHER1EGFR negative
HER1EGFR unknown
1
082 07-10 569
087 07-11 463056 04-08 106
094 06-14 138078 06-09 431
070 05-09 258098 08-13 296
074 06-09 298096 07-13 271
074 06-10 301093 07-12 268
071 05-09 211079 05-12 117096 07-13 241
073 04-12 74077 05-13 71086 07-11 424
Fact
ors
Moore et al JCO 2007
ADVANCED DISEASE
Events
Tarceva () n=282
Placebo () n=280
Any Grade 34 Any Grade 34Rash 72 6 29 1Diarrhoea 56 6 41 2Infection 43 17 34 16Stomatitis 23 lt1 14 0Pneumonitis 2 2 1 lt1Fatigue 89 15 86 15
PA3 studyPA3 study Adverse eventsAdverse events
Moore et al JCO 2007
ADVANCED DISEASE
AccetableAccetable standard standard systemicsystemic treatmenttreatment options 2009options 2009
bullbull GEM GEM alonealonebullbull GEMGEM--erlotiniberlotinib
ndashndash registredregistred for for metastaticmetastatic PC PC onlyonly mOSmOS + 12 + 12 daysdays somesome additionaladditional toxicitytoxicity
bullbull GEMGEM--CAP CAP mOSmOS + 1 + 1 monthmonth onlyonly significantsignificant in in metameta--analysisanalysis
bullbull GEMGEM--platinumplatinum ndashndash doubtfuldoubtful effecteffect -- nownow not not significantsignificant in in metameta--
analysisanalysis significantsignificant toxicitytoxicity
ADVANCED DISEASE
SUPPORTIVE CARESUPPORTIVE CARE
Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer
SUPPORTIVE CARE
GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)
enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009
Baggrund
VTE forekommer hos ca 10 af patienter med PC
Formaringl
Undersoslashge effekt af LMWH (Klexane) i kombination med
kemoterapi mht frekvens af VTE og mOS
Inklusion
Avanceret PC ikke tidligere kemoterapi
Karnofsky
PS gt 60
Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor
2 aringr
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al ASCO 2009
Antal af VTE 15152 i observation ndash 2160 i LMWH
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al
Konklusion
LMWH er effektiv og sikker behandling til forebyggelse af
VTE hos patienter med pancreascancer
Endelige resultater paring
mOS og mTTP
afventes
SUPPORTIVE CARE
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
LOCALLY ADVANCED DISEASE
ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT
LOCALLY ADVANCED DISEASE
LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT
LOCALLY ADVANCED DISEASE
LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT
LOCALLY ADVANCED DISEASE
Wilkowski
et al Final analysis
of a multicenter randomized
phase
II trial
comparing
three
different
chemoradiotherapy
regimens
in the treatment
of patients with
locally
advanced nonmetastatic
pancreatic
cancer ASCO 2009
Cis‐gemDag 1 8 22 29
Og cis‐gem
efter KRT
Kontinuerlig 5FU
Cis‐gemDag 18 22 2995 pt
ndashndash 3 forskellige kemo3 forskellige kemo‐‐regimer med regimer med konkomittantkonkomittant
strstraringaringlebehandling lebehandling aacuteaacute 50GY25fr 50GY25fr
LOCALLY ADVANCED DISEASE
Final analysis
of a multicenter randomized
phase
II trial
comparing
three
different
chemoradiotherapy
regimens
in the
treatment
of patients with
locally
advanced nonmetastatic
pancreatic
cancer Ralf
Wilkowski
bull 18 patienter blev opereret Fordeling ukendtbull Hoslashjere frekvens af grad 34 haeligmotologiske
bivirkninger i GC armene
bull Ingen forskel mellem 5FU og GemCis
PFSPFS((mdrmdr))
OSOS((mdrmdr))
HHaeligaeligmtoxmtox DiarreDiarre
RKTRKT--5FU5FU 44 9696 ++RKTRKT--GCGC 5656 9393 ++RKTRKT--GC + GCGC + GC 66 7373 ++
LOCALLY ADVANCED DISEASE
KonklusionerKonklusioner
bullbull StadigStadig ikkeikke afklaretafklaret omom kemokemo--radioterapiradioterapi forlforlaeligaeligngernger overlevelsenoverlevelsen i i forholdforhold tiltil kemoterapikemoterapi alenealene
bullbull IkkeIkke afklaretafklaret hvilkenhvilken kemoterapikemoterapi derder erer bedstbedst sammensammen med med radioterapiradioterapi
bullbull KemoKemo--radioterapiradioterapi kankan i i udvalgteudvalgte tilftilfaeligaeligldelde medfmedfoslashoslashrere konverteringkonvertering afaf sygdomsygdom frafra ikkeikke--resektabelresektabel tiltil resektabelresektabel men men detdet kankan kemoterapikemoterapi alenealene ogsogsaringaring
LOCALLY ADVANCED DISEASE
Herrmann 2008
LOCALLY ADVANCED DISEASE
ADVANCED DISEASEADVANCED DISEASE
AdvancedAdvanced diseasedisease
bullbull Median Median survivalsurvival untreateduntreated 33--4 4 monthsmonthsbullbull PrimaryPrimary goalsgoals of of treatmenttreatment
ndashndash Prolongation of Prolongation of survivalsurvivalndashndash ImprovementImprovement in in QoLQoL
ADVANCED DISEASE
GemcitabineGemcitabine vs 5vs 5--FUFU
Burris H et al J Clin Oncol 1997152403-2413
Gemcitabine 5-FU P
Clinical benefit response 24 5 0002 Median survival (months) 57 44 0002 Time to progression (months) 21 09 0001 6-month survival 46 31 1-year survival 18 2 Partial response 54 0 Stable disease 393 19 Composite of measurements of pain (analgesic consumption and pain intensity) Karnofsky
performance status and weight
ADVANCED DISEASE
SurvivalSurvival of of GemGem--treatedtreated patients patients accordingaccording to performance statusto performance status
Storinolo et al Cancer 1998
ADVANCED DISEASE
Combination chemotherapyCombination chemotherapy GemGem--CapCap
JCO october 2009
ADVANCED DISEASE
CunninghamCunningham et al GEMet al GEM--CAPCAP
Hazard ratio 080 95 CI 065ndash098Log-rank p=0026
Eur J Cancer Suppl 2005
Interim analysis 2005Final analysis 2009
ADVANCED DISEASE
MetaMeta--analysisanalysis of GEMof GEM--CAPCAP
Cunningham et al JCO 2009
ADVANCED DISEASE
Gem vs Gem vs GemGem‐‐platinumplatinumDi Miao A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
ASCO 2009
Gemcitabin
som kontrol +
cisplatin
ugentlig 25mgm2N=201
Gemcitabin
ugentlig i 7 uger
2 ugers pause og dag 18 15 i
4 ugers cyklusN=199
400 pt
ADVANCED DISEASE
GemGem GemCisGemCis
OSOS11‐‐year year survivalsurvivalPFSPFS
AnAnaeligaeligmimiTrombocytopeniTrombocytopeni
83 mdr 83 mdr 340 340 39 mdr 39 mdr
39392929
72 mdr 72 mdr 307 307 38 mdr38 mdr
50505757
A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma
The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
Di Miao
bull Alle endepunkter insignifikantebull Subgruppeanalyse
af PS 0 Signifikant negativ effekt
bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant
efter inklusion af dette studium
ADVANCED DISEASE
CombinationCombination chemotherapychemotherapy and and effecteffect accordingaccording to to performance statusperformance status
Heinemann et al BMC Cancer 2008
ADVANCED DISEASE
PA3 study GemPA3 study Gem--erlotiniberlotinib Overall survivalOverall survival
10090807060504030201
0
Surv
ival
pro
babi
lity
0 6 12 18 24Survival (months)
Tarcevatrade gemcitabine
(n=285)
Placebo gemcitabine
(n=284)
Median survival (months) 637 591
1-year survival 24 17
HR=079 (95 CI 066-095) P=0011 (adjusted for PS and extent of disease at randomization)
TarcevaTM + gemcitabinePlacebo + gemcitabine
Moore et al JCO 2007
ADVANCED DISEASE
PA3 studyPA3 study Hazard ratios for survivalHazard ratios for survival
HR 95 CI n
Tarcevaplacebo
Performance status 0-1Performance status 2
Locally advancedDistant metastasis
Pain 20 Pain gt20
MaleFemale
Age lt65Age 65
United StatesCanada
Rest of World
HER1EGFR positiveHER1EGFR negative
HER1EGFR unknown
1
082 07-10 569
087 07-11 463056 04-08 106
094 06-14 138078 06-09 431
070 05-09 258098 08-13 296
074 06-09 298096 07-13 271
074 06-10 301093 07-12 268
071 05-09 211079 05-12 117096 07-13 241
073 04-12 74077 05-13 71086 07-11 424
Fact
ors
Moore et al JCO 2007
ADVANCED DISEASE
Events
Tarceva () n=282
Placebo () n=280
Any Grade 34 Any Grade 34Rash 72 6 29 1Diarrhoea 56 6 41 2Infection 43 17 34 16Stomatitis 23 lt1 14 0Pneumonitis 2 2 1 lt1Fatigue 89 15 86 15
PA3 studyPA3 study Adverse eventsAdverse events
Moore et al JCO 2007
ADVANCED DISEASE
AccetableAccetable standard standard systemicsystemic treatmenttreatment options 2009options 2009
bullbull GEM GEM alonealonebullbull GEMGEM--erlotiniberlotinib
ndashndash registredregistred for for metastaticmetastatic PC PC onlyonly mOSmOS + 12 + 12 daysdays somesome additionaladditional toxicitytoxicity
bullbull GEMGEM--CAP CAP mOSmOS + 1 + 1 monthmonth onlyonly significantsignificant in in metameta--analysisanalysis
bullbull GEMGEM--platinumplatinum ndashndash doubtfuldoubtful effecteffect -- nownow not not significantsignificant in in metameta--
analysisanalysis significantsignificant toxicitytoxicity
ADVANCED DISEASE
SUPPORTIVE CARESUPPORTIVE CARE
Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer
SUPPORTIVE CARE
GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)
enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009
Baggrund
VTE forekommer hos ca 10 af patienter med PC
Formaringl
Undersoslashge effekt af LMWH (Klexane) i kombination med
kemoterapi mht frekvens af VTE og mOS
Inklusion
Avanceret PC ikke tidligere kemoterapi
Karnofsky
PS gt 60
Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor
2 aringr
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al ASCO 2009
Antal af VTE 15152 i observation ndash 2160 i LMWH
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al
Konklusion
LMWH er effektiv og sikker behandling til forebyggelse af
VTE hos patienter med pancreascancer
Endelige resultater paring
mOS og mTTP
afventes
SUPPORTIVE CARE
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
ChauffertChauffert et alet al Phase IIIPhase III--study of Gem vs 5FUcisplatinstudy of Gem vs 5FUcisplatin--based CRTbased CRT
LOCALLY ADVANCED DISEASE
LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT
LOCALLY ADVANCED DISEASE
LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT
LOCALLY ADVANCED DISEASE
Wilkowski
et al Final analysis
of a multicenter randomized
phase
II trial
comparing
three
different
chemoradiotherapy
regimens
in the treatment
of patients with
locally
advanced nonmetastatic
pancreatic
cancer ASCO 2009
Cis‐gemDag 1 8 22 29
Og cis‐gem
efter KRT
Kontinuerlig 5FU
Cis‐gemDag 18 22 2995 pt
ndashndash 3 forskellige kemo3 forskellige kemo‐‐regimer med regimer med konkomittantkonkomittant
strstraringaringlebehandling lebehandling aacuteaacute 50GY25fr 50GY25fr
LOCALLY ADVANCED DISEASE
Final analysis
of a multicenter randomized
phase
II trial
comparing
three
different
chemoradiotherapy
regimens
in the
treatment
of patients with
locally
advanced nonmetastatic
pancreatic
cancer Ralf
Wilkowski
bull 18 patienter blev opereret Fordeling ukendtbull Hoslashjere frekvens af grad 34 haeligmotologiske
bivirkninger i GC armene
bull Ingen forskel mellem 5FU og GemCis
PFSPFS((mdrmdr))
OSOS((mdrmdr))
HHaeligaeligmtoxmtox DiarreDiarre
RKTRKT--5FU5FU 44 9696 ++RKTRKT--GCGC 5656 9393 ++RKTRKT--GC + GCGC + GC 66 7373 ++
LOCALLY ADVANCED DISEASE
KonklusionerKonklusioner
bullbull StadigStadig ikkeikke afklaretafklaret omom kemokemo--radioterapiradioterapi forlforlaeligaeligngernger overlevelsenoverlevelsen i i forholdforhold tiltil kemoterapikemoterapi alenealene
bullbull IkkeIkke afklaretafklaret hvilkenhvilken kemoterapikemoterapi derder erer bedstbedst sammensammen med med radioterapiradioterapi
bullbull KemoKemo--radioterapiradioterapi kankan i i udvalgteudvalgte tilftilfaeligaeligldelde medfmedfoslashoslashrere konverteringkonvertering afaf sygdomsygdom frafra ikkeikke--resektabelresektabel tiltil resektabelresektabel men men detdet kankan kemoterapikemoterapi alenealene ogsogsaringaring
LOCALLY ADVANCED DISEASE
Herrmann 2008
LOCALLY ADVANCED DISEASE
ADVANCED DISEASEADVANCED DISEASE
AdvancedAdvanced diseasedisease
bullbull Median Median survivalsurvival untreateduntreated 33--4 4 monthsmonthsbullbull PrimaryPrimary goalsgoals of of treatmenttreatment
ndashndash Prolongation of Prolongation of survivalsurvivalndashndash ImprovementImprovement in in QoLQoL
ADVANCED DISEASE
GemcitabineGemcitabine vs 5vs 5--FUFU
Burris H et al J Clin Oncol 1997152403-2413
Gemcitabine 5-FU P
Clinical benefit response 24 5 0002 Median survival (months) 57 44 0002 Time to progression (months) 21 09 0001 6-month survival 46 31 1-year survival 18 2 Partial response 54 0 Stable disease 393 19 Composite of measurements of pain (analgesic consumption and pain intensity) Karnofsky
performance status and weight
ADVANCED DISEASE
SurvivalSurvival of of GemGem--treatedtreated patients patients accordingaccording to performance statusto performance status
Storinolo et al Cancer 1998
ADVANCED DISEASE
Combination chemotherapyCombination chemotherapy GemGem--CapCap
JCO october 2009
ADVANCED DISEASE
CunninghamCunningham et al GEMet al GEM--CAPCAP
Hazard ratio 080 95 CI 065ndash098Log-rank p=0026
Eur J Cancer Suppl 2005
Interim analysis 2005Final analysis 2009
ADVANCED DISEASE
MetaMeta--analysisanalysis of GEMof GEM--CAPCAP
Cunningham et al JCO 2009
ADVANCED DISEASE
Gem vs Gem vs GemGem‐‐platinumplatinumDi Miao A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
ASCO 2009
Gemcitabin
som kontrol +
cisplatin
ugentlig 25mgm2N=201
Gemcitabin
ugentlig i 7 uger
2 ugers pause og dag 18 15 i
4 ugers cyklusN=199
400 pt
ADVANCED DISEASE
GemGem GemCisGemCis
OSOS11‐‐year year survivalsurvivalPFSPFS
AnAnaeligaeligmimiTrombocytopeniTrombocytopeni
83 mdr 83 mdr 340 340 39 mdr 39 mdr
39392929
72 mdr 72 mdr 307 307 38 mdr38 mdr
50505757
A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma
The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
Di Miao
bull Alle endepunkter insignifikantebull Subgruppeanalyse
af PS 0 Signifikant negativ effekt
bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant
efter inklusion af dette studium
ADVANCED DISEASE
CombinationCombination chemotherapychemotherapy and and effecteffect accordingaccording to to performance statusperformance status
Heinemann et al BMC Cancer 2008
ADVANCED DISEASE
PA3 study GemPA3 study Gem--erlotiniberlotinib Overall survivalOverall survival
10090807060504030201
0
Surv
ival
pro
babi
lity
0 6 12 18 24Survival (months)
Tarcevatrade gemcitabine
(n=285)
Placebo gemcitabine
(n=284)
Median survival (months) 637 591
1-year survival 24 17
HR=079 (95 CI 066-095) P=0011 (adjusted for PS and extent of disease at randomization)
TarcevaTM + gemcitabinePlacebo + gemcitabine
Moore et al JCO 2007
ADVANCED DISEASE
PA3 studyPA3 study Hazard ratios for survivalHazard ratios for survival
HR 95 CI n
Tarcevaplacebo
Performance status 0-1Performance status 2
Locally advancedDistant metastasis
Pain 20 Pain gt20
MaleFemale
Age lt65Age 65
United StatesCanada
Rest of World
HER1EGFR positiveHER1EGFR negative
HER1EGFR unknown
1
082 07-10 569
087 07-11 463056 04-08 106
094 06-14 138078 06-09 431
070 05-09 258098 08-13 296
074 06-09 298096 07-13 271
074 06-10 301093 07-12 268
071 05-09 211079 05-12 117096 07-13 241
073 04-12 74077 05-13 71086 07-11 424
Fact
ors
Moore et al JCO 2007
ADVANCED DISEASE
Events
Tarceva () n=282
Placebo () n=280
Any Grade 34 Any Grade 34Rash 72 6 29 1Diarrhoea 56 6 41 2Infection 43 17 34 16Stomatitis 23 lt1 14 0Pneumonitis 2 2 1 lt1Fatigue 89 15 86 15
PA3 studyPA3 study Adverse eventsAdverse events
Moore et al JCO 2007
ADVANCED DISEASE
AccetableAccetable standard standard systemicsystemic treatmenttreatment options 2009options 2009
bullbull GEM GEM alonealonebullbull GEMGEM--erlotiniberlotinib
ndashndash registredregistred for for metastaticmetastatic PC PC onlyonly mOSmOS + 12 + 12 daysdays somesome additionaladditional toxicitytoxicity
bullbull GEMGEM--CAP CAP mOSmOS + 1 + 1 monthmonth onlyonly significantsignificant in in metameta--analysisanalysis
bullbull GEMGEM--platinumplatinum ndashndash doubtfuldoubtful effecteffect -- nownow not not significantsignificant in in metameta--
analysisanalysis significantsignificant toxicitytoxicity
ADVANCED DISEASE
SUPPORTIVE CARESUPPORTIVE CARE
Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer
SUPPORTIVE CARE
GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)
enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009
Baggrund
VTE forekommer hos ca 10 af patienter med PC
Formaringl
Undersoslashge effekt af LMWH (Klexane) i kombination med
kemoterapi mht frekvens af VTE og mOS
Inklusion
Avanceret PC ikke tidligere kemoterapi
Karnofsky
PS gt 60
Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor
2 aringr
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al ASCO 2009
Antal af VTE 15152 i observation ndash 2160 i LMWH
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al
Konklusion
LMWH er effektiv og sikker behandling til forebyggelse af
VTE hos patienter med pancreascancer
Endelige resultater paring
mOS og mTTP
afventes
SUPPORTIVE CARE
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT
LOCALLY ADVANCED DISEASE
LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT
LOCALLY ADVANCED DISEASE
Wilkowski
et al Final analysis
of a multicenter randomized
phase
II trial
comparing
three
different
chemoradiotherapy
regimens
in the treatment
of patients with
locally
advanced nonmetastatic
pancreatic
cancer ASCO 2009
Cis‐gemDag 1 8 22 29
Og cis‐gem
efter KRT
Kontinuerlig 5FU
Cis‐gemDag 18 22 2995 pt
ndashndash 3 forskellige kemo3 forskellige kemo‐‐regimer med regimer med konkomittantkonkomittant
strstraringaringlebehandling lebehandling aacuteaacute 50GY25fr 50GY25fr
LOCALLY ADVANCED DISEASE
Final analysis
of a multicenter randomized
phase
II trial
comparing
three
different
chemoradiotherapy
regimens
in the
treatment
of patients with
locally
advanced nonmetastatic
pancreatic
cancer Ralf
Wilkowski
bull 18 patienter blev opereret Fordeling ukendtbull Hoslashjere frekvens af grad 34 haeligmotologiske
bivirkninger i GC armene
bull Ingen forskel mellem 5FU og GemCis
PFSPFS((mdrmdr))
OSOS((mdrmdr))
HHaeligaeligmtoxmtox DiarreDiarre
RKTRKT--5FU5FU 44 9696 ++RKTRKT--GCGC 5656 9393 ++RKTRKT--GC + GCGC + GC 66 7373 ++
LOCALLY ADVANCED DISEASE
KonklusionerKonklusioner
bullbull StadigStadig ikkeikke afklaretafklaret omom kemokemo--radioterapiradioterapi forlforlaeligaeligngernger overlevelsenoverlevelsen i i forholdforhold tiltil kemoterapikemoterapi alenealene
bullbull IkkeIkke afklaretafklaret hvilkenhvilken kemoterapikemoterapi derder erer bedstbedst sammensammen med med radioterapiradioterapi
bullbull KemoKemo--radioterapiradioterapi kankan i i udvalgteudvalgte tilftilfaeligaeligldelde medfmedfoslashoslashrere konverteringkonvertering afaf sygdomsygdom frafra ikkeikke--resektabelresektabel tiltil resektabelresektabel men men detdet kankan kemoterapikemoterapi alenealene ogsogsaringaring
LOCALLY ADVANCED DISEASE
Herrmann 2008
LOCALLY ADVANCED DISEASE
ADVANCED DISEASEADVANCED DISEASE
AdvancedAdvanced diseasedisease
bullbull Median Median survivalsurvival untreateduntreated 33--4 4 monthsmonthsbullbull PrimaryPrimary goalsgoals of of treatmenttreatment
ndashndash Prolongation of Prolongation of survivalsurvivalndashndash ImprovementImprovement in in QoLQoL
ADVANCED DISEASE
GemcitabineGemcitabine vs 5vs 5--FUFU
Burris H et al J Clin Oncol 1997152403-2413
Gemcitabine 5-FU P
Clinical benefit response 24 5 0002 Median survival (months) 57 44 0002 Time to progression (months) 21 09 0001 6-month survival 46 31 1-year survival 18 2 Partial response 54 0 Stable disease 393 19 Composite of measurements of pain (analgesic consumption and pain intensity) Karnofsky
performance status and weight
ADVANCED DISEASE
SurvivalSurvival of of GemGem--treatedtreated patients patients accordingaccording to performance statusto performance status
Storinolo et al Cancer 1998
ADVANCED DISEASE
Combination chemotherapyCombination chemotherapy GemGem--CapCap
JCO october 2009
ADVANCED DISEASE
CunninghamCunningham et al GEMet al GEM--CAPCAP
Hazard ratio 080 95 CI 065ndash098Log-rank p=0026
Eur J Cancer Suppl 2005
Interim analysis 2005Final analysis 2009
ADVANCED DISEASE
MetaMeta--analysisanalysis of GEMof GEM--CAPCAP
Cunningham et al JCO 2009
ADVANCED DISEASE
Gem vs Gem vs GemGem‐‐platinumplatinumDi Miao A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
ASCO 2009
Gemcitabin
som kontrol +
cisplatin
ugentlig 25mgm2N=201
Gemcitabin
ugentlig i 7 uger
2 ugers pause og dag 18 15 i
4 ugers cyklusN=199
400 pt
ADVANCED DISEASE
GemGem GemCisGemCis
OSOS11‐‐year year survivalsurvivalPFSPFS
AnAnaeligaeligmimiTrombocytopeniTrombocytopeni
83 mdr 83 mdr 340 340 39 mdr 39 mdr
39392929
72 mdr 72 mdr 307 307 38 mdr38 mdr
50505757
A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma
The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
Di Miao
bull Alle endepunkter insignifikantebull Subgruppeanalyse
af PS 0 Signifikant negativ effekt
bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant
efter inklusion af dette studium
ADVANCED DISEASE
CombinationCombination chemotherapychemotherapy and and effecteffect accordingaccording to to performance statusperformance status
Heinemann et al BMC Cancer 2008
ADVANCED DISEASE
PA3 study GemPA3 study Gem--erlotiniberlotinib Overall survivalOverall survival
10090807060504030201
0
Surv
ival
pro
babi
lity
0 6 12 18 24Survival (months)
Tarcevatrade gemcitabine
(n=285)
Placebo gemcitabine
(n=284)
Median survival (months) 637 591
1-year survival 24 17
HR=079 (95 CI 066-095) P=0011 (adjusted for PS and extent of disease at randomization)
TarcevaTM + gemcitabinePlacebo + gemcitabine
Moore et al JCO 2007
ADVANCED DISEASE
PA3 studyPA3 study Hazard ratios for survivalHazard ratios for survival
HR 95 CI n
Tarcevaplacebo
Performance status 0-1Performance status 2
Locally advancedDistant metastasis
Pain 20 Pain gt20
MaleFemale
Age lt65Age 65
United StatesCanada
Rest of World
HER1EGFR positiveHER1EGFR negative
HER1EGFR unknown
1
082 07-10 569
087 07-11 463056 04-08 106
094 06-14 138078 06-09 431
070 05-09 258098 08-13 296
074 06-09 298096 07-13 271
074 06-10 301093 07-12 268
071 05-09 211079 05-12 117096 07-13 241
073 04-12 74077 05-13 71086 07-11 424
Fact
ors
Moore et al JCO 2007
ADVANCED DISEASE
Events
Tarceva () n=282
Placebo () n=280
Any Grade 34 Any Grade 34Rash 72 6 29 1Diarrhoea 56 6 41 2Infection 43 17 34 16Stomatitis 23 lt1 14 0Pneumonitis 2 2 1 lt1Fatigue 89 15 86 15
PA3 studyPA3 study Adverse eventsAdverse events
Moore et al JCO 2007
ADVANCED DISEASE
AccetableAccetable standard standard systemicsystemic treatmenttreatment options 2009options 2009
bullbull GEM GEM alonealonebullbull GEMGEM--erlotiniberlotinib
ndashndash registredregistred for for metastaticmetastatic PC PC onlyonly mOSmOS + 12 + 12 daysdays somesome additionaladditional toxicitytoxicity
bullbull GEMGEM--CAP CAP mOSmOS + 1 + 1 monthmonth onlyonly significantsignificant in in metameta--analysisanalysis
bullbull GEMGEM--platinumplatinum ndashndash doubtfuldoubtful effecteffect -- nownow not not significantsignificant in in metameta--
analysisanalysis significantsignificant toxicitytoxicity
ADVANCED DISEASE
SUPPORTIVE CARESUPPORTIVE CARE
Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer
SUPPORTIVE CARE
GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)
enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009
Baggrund
VTE forekommer hos ca 10 af patienter med PC
Formaringl
Undersoslashge effekt af LMWH (Klexane) i kombination med
kemoterapi mht frekvens af VTE og mOS
Inklusion
Avanceret PC ikke tidligere kemoterapi
Karnofsky
PS gt 60
Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor
2 aringr
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al ASCO 2009
Antal af VTE 15152 i observation ndash 2160 i LMWH
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al
Konklusion
LMWH er effektiv og sikker behandling til forebyggelse af
VTE hos patienter med pancreascancer
Endelige resultater paring
mOS og mTTP
afventes
SUPPORTIVE CARE
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
LoehrerLoehrer et alet al Phase IIIPhase III--study of Gem vs Gemstudy of Gem vs Gem--based CRTbased CRT
LOCALLY ADVANCED DISEASE
Wilkowski
et al Final analysis
of a multicenter randomized
phase
II trial
comparing
three
different
chemoradiotherapy
regimens
in the treatment
of patients with
locally
advanced nonmetastatic
pancreatic
cancer ASCO 2009
Cis‐gemDag 1 8 22 29
Og cis‐gem
efter KRT
Kontinuerlig 5FU
Cis‐gemDag 18 22 2995 pt
ndashndash 3 forskellige kemo3 forskellige kemo‐‐regimer med regimer med konkomittantkonkomittant
strstraringaringlebehandling lebehandling aacuteaacute 50GY25fr 50GY25fr
LOCALLY ADVANCED DISEASE
Final analysis
of a multicenter randomized
phase
II trial
comparing
three
different
chemoradiotherapy
regimens
in the
treatment
of patients with
locally
advanced nonmetastatic
pancreatic
cancer Ralf
Wilkowski
bull 18 patienter blev opereret Fordeling ukendtbull Hoslashjere frekvens af grad 34 haeligmotologiske
bivirkninger i GC armene
bull Ingen forskel mellem 5FU og GemCis
PFSPFS((mdrmdr))
OSOS((mdrmdr))
HHaeligaeligmtoxmtox DiarreDiarre
RKTRKT--5FU5FU 44 9696 ++RKTRKT--GCGC 5656 9393 ++RKTRKT--GC + GCGC + GC 66 7373 ++
LOCALLY ADVANCED DISEASE
KonklusionerKonklusioner
bullbull StadigStadig ikkeikke afklaretafklaret omom kemokemo--radioterapiradioterapi forlforlaeligaeligngernger overlevelsenoverlevelsen i i forholdforhold tiltil kemoterapikemoterapi alenealene
bullbull IkkeIkke afklaretafklaret hvilkenhvilken kemoterapikemoterapi derder erer bedstbedst sammensammen med med radioterapiradioterapi
bullbull KemoKemo--radioterapiradioterapi kankan i i udvalgteudvalgte tilftilfaeligaeligldelde medfmedfoslashoslashrere konverteringkonvertering afaf sygdomsygdom frafra ikkeikke--resektabelresektabel tiltil resektabelresektabel men men detdet kankan kemoterapikemoterapi alenealene ogsogsaringaring
LOCALLY ADVANCED DISEASE
Herrmann 2008
LOCALLY ADVANCED DISEASE
ADVANCED DISEASEADVANCED DISEASE
AdvancedAdvanced diseasedisease
bullbull Median Median survivalsurvival untreateduntreated 33--4 4 monthsmonthsbullbull PrimaryPrimary goalsgoals of of treatmenttreatment
ndashndash Prolongation of Prolongation of survivalsurvivalndashndash ImprovementImprovement in in QoLQoL
ADVANCED DISEASE
GemcitabineGemcitabine vs 5vs 5--FUFU
Burris H et al J Clin Oncol 1997152403-2413
Gemcitabine 5-FU P
Clinical benefit response 24 5 0002 Median survival (months) 57 44 0002 Time to progression (months) 21 09 0001 6-month survival 46 31 1-year survival 18 2 Partial response 54 0 Stable disease 393 19 Composite of measurements of pain (analgesic consumption and pain intensity) Karnofsky
performance status and weight
ADVANCED DISEASE
SurvivalSurvival of of GemGem--treatedtreated patients patients accordingaccording to performance statusto performance status
Storinolo et al Cancer 1998
ADVANCED DISEASE
Combination chemotherapyCombination chemotherapy GemGem--CapCap
JCO october 2009
ADVANCED DISEASE
CunninghamCunningham et al GEMet al GEM--CAPCAP
Hazard ratio 080 95 CI 065ndash098Log-rank p=0026
Eur J Cancer Suppl 2005
Interim analysis 2005Final analysis 2009
ADVANCED DISEASE
MetaMeta--analysisanalysis of GEMof GEM--CAPCAP
Cunningham et al JCO 2009
ADVANCED DISEASE
Gem vs Gem vs GemGem‐‐platinumplatinumDi Miao A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
ASCO 2009
Gemcitabin
som kontrol +
cisplatin
ugentlig 25mgm2N=201
Gemcitabin
ugentlig i 7 uger
2 ugers pause og dag 18 15 i
4 ugers cyklusN=199
400 pt
ADVANCED DISEASE
GemGem GemCisGemCis
OSOS11‐‐year year survivalsurvivalPFSPFS
AnAnaeligaeligmimiTrombocytopeniTrombocytopeni
83 mdr 83 mdr 340 340 39 mdr 39 mdr
39392929
72 mdr 72 mdr 307 307 38 mdr38 mdr
50505757
A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma
The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
Di Miao
bull Alle endepunkter insignifikantebull Subgruppeanalyse
af PS 0 Signifikant negativ effekt
bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant
efter inklusion af dette studium
ADVANCED DISEASE
CombinationCombination chemotherapychemotherapy and and effecteffect accordingaccording to to performance statusperformance status
Heinemann et al BMC Cancer 2008
ADVANCED DISEASE
PA3 study GemPA3 study Gem--erlotiniberlotinib Overall survivalOverall survival
10090807060504030201
0
Surv
ival
pro
babi
lity
0 6 12 18 24Survival (months)
Tarcevatrade gemcitabine
(n=285)
Placebo gemcitabine
(n=284)
Median survival (months) 637 591
1-year survival 24 17
HR=079 (95 CI 066-095) P=0011 (adjusted for PS and extent of disease at randomization)
TarcevaTM + gemcitabinePlacebo + gemcitabine
Moore et al JCO 2007
ADVANCED DISEASE
PA3 studyPA3 study Hazard ratios for survivalHazard ratios for survival
HR 95 CI n
Tarcevaplacebo
Performance status 0-1Performance status 2
Locally advancedDistant metastasis
Pain 20 Pain gt20
MaleFemale
Age lt65Age 65
United StatesCanada
Rest of World
HER1EGFR positiveHER1EGFR negative
HER1EGFR unknown
1
082 07-10 569
087 07-11 463056 04-08 106
094 06-14 138078 06-09 431
070 05-09 258098 08-13 296
074 06-09 298096 07-13 271
074 06-10 301093 07-12 268
071 05-09 211079 05-12 117096 07-13 241
073 04-12 74077 05-13 71086 07-11 424
Fact
ors
Moore et al JCO 2007
ADVANCED DISEASE
Events
Tarceva () n=282
Placebo () n=280
Any Grade 34 Any Grade 34Rash 72 6 29 1Diarrhoea 56 6 41 2Infection 43 17 34 16Stomatitis 23 lt1 14 0Pneumonitis 2 2 1 lt1Fatigue 89 15 86 15
PA3 studyPA3 study Adverse eventsAdverse events
Moore et al JCO 2007
ADVANCED DISEASE
AccetableAccetable standard standard systemicsystemic treatmenttreatment options 2009options 2009
bullbull GEM GEM alonealonebullbull GEMGEM--erlotiniberlotinib
ndashndash registredregistred for for metastaticmetastatic PC PC onlyonly mOSmOS + 12 + 12 daysdays somesome additionaladditional toxicitytoxicity
bullbull GEMGEM--CAP CAP mOSmOS + 1 + 1 monthmonth onlyonly significantsignificant in in metameta--analysisanalysis
bullbull GEMGEM--platinumplatinum ndashndash doubtfuldoubtful effecteffect -- nownow not not significantsignificant in in metameta--
analysisanalysis significantsignificant toxicitytoxicity
ADVANCED DISEASE
SUPPORTIVE CARESUPPORTIVE CARE
Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer
SUPPORTIVE CARE
GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)
enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009
Baggrund
VTE forekommer hos ca 10 af patienter med PC
Formaringl
Undersoslashge effekt af LMWH (Klexane) i kombination med
kemoterapi mht frekvens af VTE og mOS
Inklusion
Avanceret PC ikke tidligere kemoterapi
Karnofsky
PS gt 60
Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor
2 aringr
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al ASCO 2009
Antal af VTE 15152 i observation ndash 2160 i LMWH
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al
Konklusion
LMWH er effektiv og sikker behandling til forebyggelse af
VTE hos patienter med pancreascancer
Endelige resultater paring
mOS og mTTP
afventes
SUPPORTIVE CARE
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
Wilkowski
et al Final analysis
of a multicenter randomized
phase
II trial
comparing
three
different
chemoradiotherapy
regimens
in the treatment
of patients with
locally
advanced nonmetastatic
pancreatic
cancer ASCO 2009
Cis‐gemDag 1 8 22 29
Og cis‐gem
efter KRT
Kontinuerlig 5FU
Cis‐gemDag 18 22 2995 pt
ndashndash 3 forskellige kemo3 forskellige kemo‐‐regimer med regimer med konkomittantkonkomittant
strstraringaringlebehandling lebehandling aacuteaacute 50GY25fr 50GY25fr
LOCALLY ADVANCED DISEASE
Final analysis
of a multicenter randomized
phase
II trial
comparing
three
different
chemoradiotherapy
regimens
in the
treatment
of patients with
locally
advanced nonmetastatic
pancreatic
cancer Ralf
Wilkowski
bull 18 patienter blev opereret Fordeling ukendtbull Hoslashjere frekvens af grad 34 haeligmotologiske
bivirkninger i GC armene
bull Ingen forskel mellem 5FU og GemCis
PFSPFS((mdrmdr))
OSOS((mdrmdr))
HHaeligaeligmtoxmtox DiarreDiarre
RKTRKT--5FU5FU 44 9696 ++RKTRKT--GCGC 5656 9393 ++RKTRKT--GC + GCGC + GC 66 7373 ++
LOCALLY ADVANCED DISEASE
KonklusionerKonklusioner
bullbull StadigStadig ikkeikke afklaretafklaret omom kemokemo--radioterapiradioterapi forlforlaeligaeligngernger overlevelsenoverlevelsen i i forholdforhold tiltil kemoterapikemoterapi alenealene
bullbull IkkeIkke afklaretafklaret hvilkenhvilken kemoterapikemoterapi derder erer bedstbedst sammensammen med med radioterapiradioterapi
bullbull KemoKemo--radioterapiradioterapi kankan i i udvalgteudvalgte tilftilfaeligaeligldelde medfmedfoslashoslashrere konverteringkonvertering afaf sygdomsygdom frafra ikkeikke--resektabelresektabel tiltil resektabelresektabel men men detdet kankan kemoterapikemoterapi alenealene ogsogsaringaring
LOCALLY ADVANCED DISEASE
Herrmann 2008
LOCALLY ADVANCED DISEASE
ADVANCED DISEASEADVANCED DISEASE
AdvancedAdvanced diseasedisease
bullbull Median Median survivalsurvival untreateduntreated 33--4 4 monthsmonthsbullbull PrimaryPrimary goalsgoals of of treatmenttreatment
ndashndash Prolongation of Prolongation of survivalsurvivalndashndash ImprovementImprovement in in QoLQoL
ADVANCED DISEASE
GemcitabineGemcitabine vs 5vs 5--FUFU
Burris H et al J Clin Oncol 1997152403-2413
Gemcitabine 5-FU P
Clinical benefit response 24 5 0002 Median survival (months) 57 44 0002 Time to progression (months) 21 09 0001 6-month survival 46 31 1-year survival 18 2 Partial response 54 0 Stable disease 393 19 Composite of measurements of pain (analgesic consumption and pain intensity) Karnofsky
performance status and weight
ADVANCED DISEASE
SurvivalSurvival of of GemGem--treatedtreated patients patients accordingaccording to performance statusto performance status
Storinolo et al Cancer 1998
ADVANCED DISEASE
Combination chemotherapyCombination chemotherapy GemGem--CapCap
JCO october 2009
ADVANCED DISEASE
CunninghamCunningham et al GEMet al GEM--CAPCAP
Hazard ratio 080 95 CI 065ndash098Log-rank p=0026
Eur J Cancer Suppl 2005
Interim analysis 2005Final analysis 2009
ADVANCED DISEASE
MetaMeta--analysisanalysis of GEMof GEM--CAPCAP
Cunningham et al JCO 2009
ADVANCED DISEASE
Gem vs Gem vs GemGem‐‐platinumplatinumDi Miao A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
ASCO 2009
Gemcitabin
som kontrol +
cisplatin
ugentlig 25mgm2N=201
Gemcitabin
ugentlig i 7 uger
2 ugers pause og dag 18 15 i
4 ugers cyklusN=199
400 pt
ADVANCED DISEASE
GemGem GemCisGemCis
OSOS11‐‐year year survivalsurvivalPFSPFS
AnAnaeligaeligmimiTrombocytopeniTrombocytopeni
83 mdr 83 mdr 340 340 39 mdr 39 mdr
39392929
72 mdr 72 mdr 307 307 38 mdr38 mdr
50505757
A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma
The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
Di Miao
bull Alle endepunkter insignifikantebull Subgruppeanalyse
af PS 0 Signifikant negativ effekt
bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant
efter inklusion af dette studium
ADVANCED DISEASE
CombinationCombination chemotherapychemotherapy and and effecteffect accordingaccording to to performance statusperformance status
Heinemann et al BMC Cancer 2008
ADVANCED DISEASE
PA3 study GemPA3 study Gem--erlotiniberlotinib Overall survivalOverall survival
10090807060504030201
0
Surv
ival
pro
babi
lity
0 6 12 18 24Survival (months)
Tarcevatrade gemcitabine
(n=285)
Placebo gemcitabine
(n=284)
Median survival (months) 637 591
1-year survival 24 17
HR=079 (95 CI 066-095) P=0011 (adjusted for PS and extent of disease at randomization)
TarcevaTM + gemcitabinePlacebo + gemcitabine
Moore et al JCO 2007
ADVANCED DISEASE
PA3 studyPA3 study Hazard ratios for survivalHazard ratios for survival
HR 95 CI n
Tarcevaplacebo
Performance status 0-1Performance status 2
Locally advancedDistant metastasis
Pain 20 Pain gt20
MaleFemale
Age lt65Age 65
United StatesCanada
Rest of World
HER1EGFR positiveHER1EGFR negative
HER1EGFR unknown
1
082 07-10 569
087 07-11 463056 04-08 106
094 06-14 138078 06-09 431
070 05-09 258098 08-13 296
074 06-09 298096 07-13 271
074 06-10 301093 07-12 268
071 05-09 211079 05-12 117096 07-13 241
073 04-12 74077 05-13 71086 07-11 424
Fact
ors
Moore et al JCO 2007
ADVANCED DISEASE
Events
Tarceva () n=282
Placebo () n=280
Any Grade 34 Any Grade 34Rash 72 6 29 1Diarrhoea 56 6 41 2Infection 43 17 34 16Stomatitis 23 lt1 14 0Pneumonitis 2 2 1 lt1Fatigue 89 15 86 15
PA3 studyPA3 study Adverse eventsAdverse events
Moore et al JCO 2007
ADVANCED DISEASE
AccetableAccetable standard standard systemicsystemic treatmenttreatment options 2009options 2009
bullbull GEM GEM alonealonebullbull GEMGEM--erlotiniberlotinib
ndashndash registredregistred for for metastaticmetastatic PC PC onlyonly mOSmOS + 12 + 12 daysdays somesome additionaladditional toxicitytoxicity
bullbull GEMGEM--CAP CAP mOSmOS + 1 + 1 monthmonth onlyonly significantsignificant in in metameta--analysisanalysis
bullbull GEMGEM--platinumplatinum ndashndash doubtfuldoubtful effecteffect -- nownow not not significantsignificant in in metameta--
analysisanalysis significantsignificant toxicitytoxicity
ADVANCED DISEASE
SUPPORTIVE CARESUPPORTIVE CARE
Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer
SUPPORTIVE CARE
GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)
enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009
Baggrund
VTE forekommer hos ca 10 af patienter med PC
Formaringl
Undersoslashge effekt af LMWH (Klexane) i kombination med
kemoterapi mht frekvens af VTE og mOS
Inklusion
Avanceret PC ikke tidligere kemoterapi
Karnofsky
PS gt 60
Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor
2 aringr
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al ASCO 2009
Antal af VTE 15152 i observation ndash 2160 i LMWH
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al
Konklusion
LMWH er effektiv og sikker behandling til forebyggelse af
VTE hos patienter med pancreascancer
Endelige resultater paring
mOS og mTTP
afventes
SUPPORTIVE CARE
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
Final analysis
of a multicenter randomized
phase
II trial
comparing
three
different
chemoradiotherapy
regimens
in the
treatment
of patients with
locally
advanced nonmetastatic
pancreatic
cancer Ralf
Wilkowski
bull 18 patienter blev opereret Fordeling ukendtbull Hoslashjere frekvens af grad 34 haeligmotologiske
bivirkninger i GC armene
bull Ingen forskel mellem 5FU og GemCis
PFSPFS((mdrmdr))
OSOS((mdrmdr))
HHaeligaeligmtoxmtox DiarreDiarre
RKTRKT--5FU5FU 44 9696 ++RKTRKT--GCGC 5656 9393 ++RKTRKT--GC + GCGC + GC 66 7373 ++
LOCALLY ADVANCED DISEASE
KonklusionerKonklusioner
bullbull StadigStadig ikkeikke afklaretafklaret omom kemokemo--radioterapiradioterapi forlforlaeligaeligngernger overlevelsenoverlevelsen i i forholdforhold tiltil kemoterapikemoterapi alenealene
bullbull IkkeIkke afklaretafklaret hvilkenhvilken kemoterapikemoterapi derder erer bedstbedst sammensammen med med radioterapiradioterapi
bullbull KemoKemo--radioterapiradioterapi kankan i i udvalgteudvalgte tilftilfaeligaeligldelde medfmedfoslashoslashrere konverteringkonvertering afaf sygdomsygdom frafra ikkeikke--resektabelresektabel tiltil resektabelresektabel men men detdet kankan kemoterapikemoterapi alenealene ogsogsaringaring
LOCALLY ADVANCED DISEASE
Herrmann 2008
LOCALLY ADVANCED DISEASE
ADVANCED DISEASEADVANCED DISEASE
AdvancedAdvanced diseasedisease
bullbull Median Median survivalsurvival untreateduntreated 33--4 4 monthsmonthsbullbull PrimaryPrimary goalsgoals of of treatmenttreatment
ndashndash Prolongation of Prolongation of survivalsurvivalndashndash ImprovementImprovement in in QoLQoL
ADVANCED DISEASE
GemcitabineGemcitabine vs 5vs 5--FUFU
Burris H et al J Clin Oncol 1997152403-2413
Gemcitabine 5-FU P
Clinical benefit response 24 5 0002 Median survival (months) 57 44 0002 Time to progression (months) 21 09 0001 6-month survival 46 31 1-year survival 18 2 Partial response 54 0 Stable disease 393 19 Composite of measurements of pain (analgesic consumption and pain intensity) Karnofsky
performance status and weight
ADVANCED DISEASE
SurvivalSurvival of of GemGem--treatedtreated patients patients accordingaccording to performance statusto performance status
Storinolo et al Cancer 1998
ADVANCED DISEASE
Combination chemotherapyCombination chemotherapy GemGem--CapCap
JCO october 2009
ADVANCED DISEASE
CunninghamCunningham et al GEMet al GEM--CAPCAP
Hazard ratio 080 95 CI 065ndash098Log-rank p=0026
Eur J Cancer Suppl 2005
Interim analysis 2005Final analysis 2009
ADVANCED DISEASE
MetaMeta--analysisanalysis of GEMof GEM--CAPCAP
Cunningham et al JCO 2009
ADVANCED DISEASE
Gem vs Gem vs GemGem‐‐platinumplatinumDi Miao A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
ASCO 2009
Gemcitabin
som kontrol +
cisplatin
ugentlig 25mgm2N=201
Gemcitabin
ugentlig i 7 uger
2 ugers pause og dag 18 15 i
4 ugers cyklusN=199
400 pt
ADVANCED DISEASE
GemGem GemCisGemCis
OSOS11‐‐year year survivalsurvivalPFSPFS
AnAnaeligaeligmimiTrombocytopeniTrombocytopeni
83 mdr 83 mdr 340 340 39 mdr 39 mdr
39392929
72 mdr 72 mdr 307 307 38 mdr38 mdr
50505757
A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma
The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
Di Miao
bull Alle endepunkter insignifikantebull Subgruppeanalyse
af PS 0 Signifikant negativ effekt
bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant
efter inklusion af dette studium
ADVANCED DISEASE
CombinationCombination chemotherapychemotherapy and and effecteffect accordingaccording to to performance statusperformance status
Heinemann et al BMC Cancer 2008
ADVANCED DISEASE
PA3 study GemPA3 study Gem--erlotiniberlotinib Overall survivalOverall survival
10090807060504030201
0
Surv
ival
pro
babi
lity
0 6 12 18 24Survival (months)
Tarcevatrade gemcitabine
(n=285)
Placebo gemcitabine
(n=284)
Median survival (months) 637 591
1-year survival 24 17
HR=079 (95 CI 066-095) P=0011 (adjusted for PS and extent of disease at randomization)
TarcevaTM + gemcitabinePlacebo + gemcitabine
Moore et al JCO 2007
ADVANCED DISEASE
PA3 studyPA3 study Hazard ratios for survivalHazard ratios for survival
HR 95 CI n
Tarcevaplacebo
Performance status 0-1Performance status 2
Locally advancedDistant metastasis
Pain 20 Pain gt20
MaleFemale
Age lt65Age 65
United StatesCanada
Rest of World
HER1EGFR positiveHER1EGFR negative
HER1EGFR unknown
1
082 07-10 569
087 07-11 463056 04-08 106
094 06-14 138078 06-09 431
070 05-09 258098 08-13 296
074 06-09 298096 07-13 271
074 06-10 301093 07-12 268
071 05-09 211079 05-12 117096 07-13 241
073 04-12 74077 05-13 71086 07-11 424
Fact
ors
Moore et al JCO 2007
ADVANCED DISEASE
Events
Tarceva () n=282
Placebo () n=280
Any Grade 34 Any Grade 34Rash 72 6 29 1Diarrhoea 56 6 41 2Infection 43 17 34 16Stomatitis 23 lt1 14 0Pneumonitis 2 2 1 lt1Fatigue 89 15 86 15
PA3 studyPA3 study Adverse eventsAdverse events
Moore et al JCO 2007
ADVANCED DISEASE
AccetableAccetable standard standard systemicsystemic treatmenttreatment options 2009options 2009
bullbull GEM GEM alonealonebullbull GEMGEM--erlotiniberlotinib
ndashndash registredregistred for for metastaticmetastatic PC PC onlyonly mOSmOS + 12 + 12 daysdays somesome additionaladditional toxicitytoxicity
bullbull GEMGEM--CAP CAP mOSmOS + 1 + 1 monthmonth onlyonly significantsignificant in in metameta--analysisanalysis
bullbull GEMGEM--platinumplatinum ndashndash doubtfuldoubtful effecteffect -- nownow not not significantsignificant in in metameta--
analysisanalysis significantsignificant toxicitytoxicity
ADVANCED DISEASE
SUPPORTIVE CARESUPPORTIVE CARE
Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer
SUPPORTIVE CARE
GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)
enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009
Baggrund
VTE forekommer hos ca 10 af patienter med PC
Formaringl
Undersoslashge effekt af LMWH (Klexane) i kombination med
kemoterapi mht frekvens af VTE og mOS
Inklusion
Avanceret PC ikke tidligere kemoterapi
Karnofsky
PS gt 60
Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor
2 aringr
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al ASCO 2009
Antal af VTE 15152 i observation ndash 2160 i LMWH
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al
Konklusion
LMWH er effektiv og sikker behandling til forebyggelse af
VTE hos patienter med pancreascancer
Endelige resultater paring
mOS og mTTP
afventes
SUPPORTIVE CARE
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
KonklusionerKonklusioner
bullbull StadigStadig ikkeikke afklaretafklaret omom kemokemo--radioterapiradioterapi forlforlaeligaeligngernger overlevelsenoverlevelsen i i forholdforhold tiltil kemoterapikemoterapi alenealene
bullbull IkkeIkke afklaretafklaret hvilkenhvilken kemoterapikemoterapi derder erer bedstbedst sammensammen med med radioterapiradioterapi
bullbull KemoKemo--radioterapiradioterapi kankan i i udvalgteudvalgte tilftilfaeligaeligldelde medfmedfoslashoslashrere konverteringkonvertering afaf sygdomsygdom frafra ikkeikke--resektabelresektabel tiltil resektabelresektabel men men detdet kankan kemoterapikemoterapi alenealene ogsogsaringaring
LOCALLY ADVANCED DISEASE
Herrmann 2008
LOCALLY ADVANCED DISEASE
ADVANCED DISEASEADVANCED DISEASE
AdvancedAdvanced diseasedisease
bullbull Median Median survivalsurvival untreateduntreated 33--4 4 monthsmonthsbullbull PrimaryPrimary goalsgoals of of treatmenttreatment
ndashndash Prolongation of Prolongation of survivalsurvivalndashndash ImprovementImprovement in in QoLQoL
ADVANCED DISEASE
GemcitabineGemcitabine vs 5vs 5--FUFU
Burris H et al J Clin Oncol 1997152403-2413
Gemcitabine 5-FU P
Clinical benefit response 24 5 0002 Median survival (months) 57 44 0002 Time to progression (months) 21 09 0001 6-month survival 46 31 1-year survival 18 2 Partial response 54 0 Stable disease 393 19 Composite of measurements of pain (analgesic consumption and pain intensity) Karnofsky
performance status and weight
ADVANCED DISEASE
SurvivalSurvival of of GemGem--treatedtreated patients patients accordingaccording to performance statusto performance status
Storinolo et al Cancer 1998
ADVANCED DISEASE
Combination chemotherapyCombination chemotherapy GemGem--CapCap
JCO october 2009
ADVANCED DISEASE
CunninghamCunningham et al GEMet al GEM--CAPCAP
Hazard ratio 080 95 CI 065ndash098Log-rank p=0026
Eur J Cancer Suppl 2005
Interim analysis 2005Final analysis 2009
ADVANCED DISEASE
MetaMeta--analysisanalysis of GEMof GEM--CAPCAP
Cunningham et al JCO 2009
ADVANCED DISEASE
Gem vs Gem vs GemGem‐‐platinumplatinumDi Miao A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
ASCO 2009
Gemcitabin
som kontrol +
cisplatin
ugentlig 25mgm2N=201
Gemcitabin
ugentlig i 7 uger
2 ugers pause og dag 18 15 i
4 ugers cyklusN=199
400 pt
ADVANCED DISEASE
GemGem GemCisGemCis
OSOS11‐‐year year survivalsurvivalPFSPFS
AnAnaeligaeligmimiTrombocytopeniTrombocytopeni
83 mdr 83 mdr 340 340 39 mdr 39 mdr
39392929
72 mdr 72 mdr 307 307 38 mdr38 mdr
50505757
A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma
The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
Di Miao
bull Alle endepunkter insignifikantebull Subgruppeanalyse
af PS 0 Signifikant negativ effekt
bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant
efter inklusion af dette studium
ADVANCED DISEASE
CombinationCombination chemotherapychemotherapy and and effecteffect accordingaccording to to performance statusperformance status
Heinemann et al BMC Cancer 2008
ADVANCED DISEASE
PA3 study GemPA3 study Gem--erlotiniberlotinib Overall survivalOverall survival
10090807060504030201
0
Surv
ival
pro
babi
lity
0 6 12 18 24Survival (months)
Tarcevatrade gemcitabine
(n=285)
Placebo gemcitabine
(n=284)
Median survival (months) 637 591
1-year survival 24 17
HR=079 (95 CI 066-095) P=0011 (adjusted for PS and extent of disease at randomization)
TarcevaTM + gemcitabinePlacebo + gemcitabine
Moore et al JCO 2007
ADVANCED DISEASE
PA3 studyPA3 study Hazard ratios for survivalHazard ratios for survival
HR 95 CI n
Tarcevaplacebo
Performance status 0-1Performance status 2
Locally advancedDistant metastasis
Pain 20 Pain gt20
MaleFemale
Age lt65Age 65
United StatesCanada
Rest of World
HER1EGFR positiveHER1EGFR negative
HER1EGFR unknown
1
082 07-10 569
087 07-11 463056 04-08 106
094 06-14 138078 06-09 431
070 05-09 258098 08-13 296
074 06-09 298096 07-13 271
074 06-10 301093 07-12 268
071 05-09 211079 05-12 117096 07-13 241
073 04-12 74077 05-13 71086 07-11 424
Fact
ors
Moore et al JCO 2007
ADVANCED DISEASE
Events
Tarceva () n=282
Placebo () n=280
Any Grade 34 Any Grade 34Rash 72 6 29 1Diarrhoea 56 6 41 2Infection 43 17 34 16Stomatitis 23 lt1 14 0Pneumonitis 2 2 1 lt1Fatigue 89 15 86 15
PA3 studyPA3 study Adverse eventsAdverse events
Moore et al JCO 2007
ADVANCED DISEASE
AccetableAccetable standard standard systemicsystemic treatmenttreatment options 2009options 2009
bullbull GEM GEM alonealonebullbull GEMGEM--erlotiniberlotinib
ndashndash registredregistred for for metastaticmetastatic PC PC onlyonly mOSmOS + 12 + 12 daysdays somesome additionaladditional toxicitytoxicity
bullbull GEMGEM--CAP CAP mOSmOS + 1 + 1 monthmonth onlyonly significantsignificant in in metameta--analysisanalysis
bullbull GEMGEM--platinumplatinum ndashndash doubtfuldoubtful effecteffect -- nownow not not significantsignificant in in metameta--
analysisanalysis significantsignificant toxicitytoxicity
ADVANCED DISEASE
SUPPORTIVE CARESUPPORTIVE CARE
Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer
SUPPORTIVE CARE
GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)
enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009
Baggrund
VTE forekommer hos ca 10 af patienter med PC
Formaringl
Undersoslashge effekt af LMWH (Klexane) i kombination med
kemoterapi mht frekvens af VTE og mOS
Inklusion
Avanceret PC ikke tidligere kemoterapi
Karnofsky
PS gt 60
Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor
2 aringr
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al ASCO 2009
Antal af VTE 15152 i observation ndash 2160 i LMWH
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al
Konklusion
LMWH er effektiv og sikker behandling til forebyggelse af
VTE hos patienter med pancreascancer
Endelige resultater paring
mOS og mTTP
afventes
SUPPORTIVE CARE
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
Herrmann 2008
LOCALLY ADVANCED DISEASE
ADVANCED DISEASEADVANCED DISEASE
AdvancedAdvanced diseasedisease
bullbull Median Median survivalsurvival untreateduntreated 33--4 4 monthsmonthsbullbull PrimaryPrimary goalsgoals of of treatmenttreatment
ndashndash Prolongation of Prolongation of survivalsurvivalndashndash ImprovementImprovement in in QoLQoL
ADVANCED DISEASE
GemcitabineGemcitabine vs 5vs 5--FUFU
Burris H et al J Clin Oncol 1997152403-2413
Gemcitabine 5-FU P
Clinical benefit response 24 5 0002 Median survival (months) 57 44 0002 Time to progression (months) 21 09 0001 6-month survival 46 31 1-year survival 18 2 Partial response 54 0 Stable disease 393 19 Composite of measurements of pain (analgesic consumption and pain intensity) Karnofsky
performance status and weight
ADVANCED DISEASE
SurvivalSurvival of of GemGem--treatedtreated patients patients accordingaccording to performance statusto performance status
Storinolo et al Cancer 1998
ADVANCED DISEASE
Combination chemotherapyCombination chemotherapy GemGem--CapCap
JCO october 2009
ADVANCED DISEASE
CunninghamCunningham et al GEMet al GEM--CAPCAP
Hazard ratio 080 95 CI 065ndash098Log-rank p=0026
Eur J Cancer Suppl 2005
Interim analysis 2005Final analysis 2009
ADVANCED DISEASE
MetaMeta--analysisanalysis of GEMof GEM--CAPCAP
Cunningham et al JCO 2009
ADVANCED DISEASE
Gem vs Gem vs GemGem‐‐platinumplatinumDi Miao A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
ASCO 2009
Gemcitabin
som kontrol +
cisplatin
ugentlig 25mgm2N=201
Gemcitabin
ugentlig i 7 uger
2 ugers pause og dag 18 15 i
4 ugers cyklusN=199
400 pt
ADVANCED DISEASE
GemGem GemCisGemCis
OSOS11‐‐year year survivalsurvivalPFSPFS
AnAnaeligaeligmimiTrombocytopeniTrombocytopeni
83 mdr 83 mdr 340 340 39 mdr 39 mdr
39392929
72 mdr 72 mdr 307 307 38 mdr38 mdr
50505757
A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma
The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
Di Miao
bull Alle endepunkter insignifikantebull Subgruppeanalyse
af PS 0 Signifikant negativ effekt
bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant
efter inklusion af dette studium
ADVANCED DISEASE
CombinationCombination chemotherapychemotherapy and and effecteffect accordingaccording to to performance statusperformance status
Heinemann et al BMC Cancer 2008
ADVANCED DISEASE
PA3 study GemPA3 study Gem--erlotiniberlotinib Overall survivalOverall survival
10090807060504030201
0
Surv
ival
pro
babi
lity
0 6 12 18 24Survival (months)
Tarcevatrade gemcitabine
(n=285)
Placebo gemcitabine
(n=284)
Median survival (months) 637 591
1-year survival 24 17
HR=079 (95 CI 066-095) P=0011 (adjusted for PS and extent of disease at randomization)
TarcevaTM + gemcitabinePlacebo + gemcitabine
Moore et al JCO 2007
ADVANCED DISEASE
PA3 studyPA3 study Hazard ratios for survivalHazard ratios for survival
HR 95 CI n
Tarcevaplacebo
Performance status 0-1Performance status 2
Locally advancedDistant metastasis
Pain 20 Pain gt20
MaleFemale
Age lt65Age 65
United StatesCanada
Rest of World
HER1EGFR positiveHER1EGFR negative
HER1EGFR unknown
1
082 07-10 569
087 07-11 463056 04-08 106
094 06-14 138078 06-09 431
070 05-09 258098 08-13 296
074 06-09 298096 07-13 271
074 06-10 301093 07-12 268
071 05-09 211079 05-12 117096 07-13 241
073 04-12 74077 05-13 71086 07-11 424
Fact
ors
Moore et al JCO 2007
ADVANCED DISEASE
Events
Tarceva () n=282
Placebo () n=280
Any Grade 34 Any Grade 34Rash 72 6 29 1Diarrhoea 56 6 41 2Infection 43 17 34 16Stomatitis 23 lt1 14 0Pneumonitis 2 2 1 lt1Fatigue 89 15 86 15
PA3 studyPA3 study Adverse eventsAdverse events
Moore et al JCO 2007
ADVANCED DISEASE
AccetableAccetable standard standard systemicsystemic treatmenttreatment options 2009options 2009
bullbull GEM GEM alonealonebullbull GEMGEM--erlotiniberlotinib
ndashndash registredregistred for for metastaticmetastatic PC PC onlyonly mOSmOS + 12 + 12 daysdays somesome additionaladditional toxicitytoxicity
bullbull GEMGEM--CAP CAP mOSmOS + 1 + 1 monthmonth onlyonly significantsignificant in in metameta--analysisanalysis
bullbull GEMGEM--platinumplatinum ndashndash doubtfuldoubtful effecteffect -- nownow not not significantsignificant in in metameta--
analysisanalysis significantsignificant toxicitytoxicity
ADVANCED DISEASE
SUPPORTIVE CARESUPPORTIVE CARE
Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer
SUPPORTIVE CARE
GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)
enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009
Baggrund
VTE forekommer hos ca 10 af patienter med PC
Formaringl
Undersoslashge effekt af LMWH (Klexane) i kombination med
kemoterapi mht frekvens af VTE og mOS
Inklusion
Avanceret PC ikke tidligere kemoterapi
Karnofsky
PS gt 60
Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor
2 aringr
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al ASCO 2009
Antal af VTE 15152 i observation ndash 2160 i LMWH
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al
Konklusion
LMWH er effektiv og sikker behandling til forebyggelse af
VTE hos patienter med pancreascancer
Endelige resultater paring
mOS og mTTP
afventes
SUPPORTIVE CARE
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
ADVANCED DISEASEADVANCED DISEASE
AdvancedAdvanced diseasedisease
bullbull Median Median survivalsurvival untreateduntreated 33--4 4 monthsmonthsbullbull PrimaryPrimary goalsgoals of of treatmenttreatment
ndashndash Prolongation of Prolongation of survivalsurvivalndashndash ImprovementImprovement in in QoLQoL
ADVANCED DISEASE
GemcitabineGemcitabine vs 5vs 5--FUFU
Burris H et al J Clin Oncol 1997152403-2413
Gemcitabine 5-FU P
Clinical benefit response 24 5 0002 Median survival (months) 57 44 0002 Time to progression (months) 21 09 0001 6-month survival 46 31 1-year survival 18 2 Partial response 54 0 Stable disease 393 19 Composite of measurements of pain (analgesic consumption and pain intensity) Karnofsky
performance status and weight
ADVANCED DISEASE
SurvivalSurvival of of GemGem--treatedtreated patients patients accordingaccording to performance statusto performance status
Storinolo et al Cancer 1998
ADVANCED DISEASE
Combination chemotherapyCombination chemotherapy GemGem--CapCap
JCO october 2009
ADVANCED DISEASE
CunninghamCunningham et al GEMet al GEM--CAPCAP
Hazard ratio 080 95 CI 065ndash098Log-rank p=0026
Eur J Cancer Suppl 2005
Interim analysis 2005Final analysis 2009
ADVANCED DISEASE
MetaMeta--analysisanalysis of GEMof GEM--CAPCAP
Cunningham et al JCO 2009
ADVANCED DISEASE
Gem vs Gem vs GemGem‐‐platinumplatinumDi Miao A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
ASCO 2009
Gemcitabin
som kontrol +
cisplatin
ugentlig 25mgm2N=201
Gemcitabin
ugentlig i 7 uger
2 ugers pause og dag 18 15 i
4 ugers cyklusN=199
400 pt
ADVANCED DISEASE
GemGem GemCisGemCis
OSOS11‐‐year year survivalsurvivalPFSPFS
AnAnaeligaeligmimiTrombocytopeniTrombocytopeni
83 mdr 83 mdr 340 340 39 mdr 39 mdr
39392929
72 mdr 72 mdr 307 307 38 mdr38 mdr
50505757
A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma
The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
Di Miao
bull Alle endepunkter insignifikantebull Subgruppeanalyse
af PS 0 Signifikant negativ effekt
bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant
efter inklusion af dette studium
ADVANCED DISEASE
CombinationCombination chemotherapychemotherapy and and effecteffect accordingaccording to to performance statusperformance status
Heinemann et al BMC Cancer 2008
ADVANCED DISEASE
PA3 study GemPA3 study Gem--erlotiniberlotinib Overall survivalOverall survival
10090807060504030201
0
Surv
ival
pro
babi
lity
0 6 12 18 24Survival (months)
Tarcevatrade gemcitabine
(n=285)
Placebo gemcitabine
(n=284)
Median survival (months) 637 591
1-year survival 24 17
HR=079 (95 CI 066-095) P=0011 (adjusted for PS and extent of disease at randomization)
TarcevaTM + gemcitabinePlacebo + gemcitabine
Moore et al JCO 2007
ADVANCED DISEASE
PA3 studyPA3 study Hazard ratios for survivalHazard ratios for survival
HR 95 CI n
Tarcevaplacebo
Performance status 0-1Performance status 2
Locally advancedDistant metastasis
Pain 20 Pain gt20
MaleFemale
Age lt65Age 65
United StatesCanada
Rest of World
HER1EGFR positiveHER1EGFR negative
HER1EGFR unknown
1
082 07-10 569
087 07-11 463056 04-08 106
094 06-14 138078 06-09 431
070 05-09 258098 08-13 296
074 06-09 298096 07-13 271
074 06-10 301093 07-12 268
071 05-09 211079 05-12 117096 07-13 241
073 04-12 74077 05-13 71086 07-11 424
Fact
ors
Moore et al JCO 2007
ADVANCED DISEASE
Events
Tarceva () n=282
Placebo () n=280
Any Grade 34 Any Grade 34Rash 72 6 29 1Diarrhoea 56 6 41 2Infection 43 17 34 16Stomatitis 23 lt1 14 0Pneumonitis 2 2 1 lt1Fatigue 89 15 86 15
PA3 studyPA3 study Adverse eventsAdverse events
Moore et al JCO 2007
ADVANCED DISEASE
AccetableAccetable standard standard systemicsystemic treatmenttreatment options 2009options 2009
bullbull GEM GEM alonealonebullbull GEMGEM--erlotiniberlotinib
ndashndash registredregistred for for metastaticmetastatic PC PC onlyonly mOSmOS + 12 + 12 daysdays somesome additionaladditional toxicitytoxicity
bullbull GEMGEM--CAP CAP mOSmOS + 1 + 1 monthmonth onlyonly significantsignificant in in metameta--analysisanalysis
bullbull GEMGEM--platinumplatinum ndashndash doubtfuldoubtful effecteffect -- nownow not not significantsignificant in in metameta--
analysisanalysis significantsignificant toxicitytoxicity
ADVANCED DISEASE
SUPPORTIVE CARESUPPORTIVE CARE
Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer
SUPPORTIVE CARE
GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)
enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009
Baggrund
VTE forekommer hos ca 10 af patienter med PC
Formaringl
Undersoslashge effekt af LMWH (Klexane) i kombination med
kemoterapi mht frekvens af VTE og mOS
Inklusion
Avanceret PC ikke tidligere kemoterapi
Karnofsky
PS gt 60
Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor
2 aringr
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al ASCO 2009
Antal af VTE 15152 i observation ndash 2160 i LMWH
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al
Konklusion
LMWH er effektiv og sikker behandling til forebyggelse af
VTE hos patienter med pancreascancer
Endelige resultater paring
mOS og mTTP
afventes
SUPPORTIVE CARE
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
AdvancedAdvanced diseasedisease
bullbull Median Median survivalsurvival untreateduntreated 33--4 4 monthsmonthsbullbull PrimaryPrimary goalsgoals of of treatmenttreatment
ndashndash Prolongation of Prolongation of survivalsurvivalndashndash ImprovementImprovement in in QoLQoL
ADVANCED DISEASE
GemcitabineGemcitabine vs 5vs 5--FUFU
Burris H et al J Clin Oncol 1997152403-2413
Gemcitabine 5-FU P
Clinical benefit response 24 5 0002 Median survival (months) 57 44 0002 Time to progression (months) 21 09 0001 6-month survival 46 31 1-year survival 18 2 Partial response 54 0 Stable disease 393 19 Composite of measurements of pain (analgesic consumption and pain intensity) Karnofsky
performance status and weight
ADVANCED DISEASE
SurvivalSurvival of of GemGem--treatedtreated patients patients accordingaccording to performance statusto performance status
Storinolo et al Cancer 1998
ADVANCED DISEASE
Combination chemotherapyCombination chemotherapy GemGem--CapCap
JCO october 2009
ADVANCED DISEASE
CunninghamCunningham et al GEMet al GEM--CAPCAP
Hazard ratio 080 95 CI 065ndash098Log-rank p=0026
Eur J Cancer Suppl 2005
Interim analysis 2005Final analysis 2009
ADVANCED DISEASE
MetaMeta--analysisanalysis of GEMof GEM--CAPCAP
Cunningham et al JCO 2009
ADVANCED DISEASE
Gem vs Gem vs GemGem‐‐platinumplatinumDi Miao A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
ASCO 2009
Gemcitabin
som kontrol +
cisplatin
ugentlig 25mgm2N=201
Gemcitabin
ugentlig i 7 uger
2 ugers pause og dag 18 15 i
4 ugers cyklusN=199
400 pt
ADVANCED DISEASE
GemGem GemCisGemCis
OSOS11‐‐year year survivalsurvivalPFSPFS
AnAnaeligaeligmimiTrombocytopeniTrombocytopeni
83 mdr 83 mdr 340 340 39 mdr 39 mdr
39392929
72 mdr 72 mdr 307 307 38 mdr38 mdr
50505757
A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma
The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
Di Miao
bull Alle endepunkter insignifikantebull Subgruppeanalyse
af PS 0 Signifikant negativ effekt
bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant
efter inklusion af dette studium
ADVANCED DISEASE
CombinationCombination chemotherapychemotherapy and and effecteffect accordingaccording to to performance statusperformance status
Heinemann et al BMC Cancer 2008
ADVANCED DISEASE
PA3 study GemPA3 study Gem--erlotiniberlotinib Overall survivalOverall survival
10090807060504030201
0
Surv
ival
pro
babi
lity
0 6 12 18 24Survival (months)
Tarcevatrade gemcitabine
(n=285)
Placebo gemcitabine
(n=284)
Median survival (months) 637 591
1-year survival 24 17
HR=079 (95 CI 066-095) P=0011 (adjusted for PS and extent of disease at randomization)
TarcevaTM + gemcitabinePlacebo + gemcitabine
Moore et al JCO 2007
ADVANCED DISEASE
PA3 studyPA3 study Hazard ratios for survivalHazard ratios for survival
HR 95 CI n
Tarcevaplacebo
Performance status 0-1Performance status 2
Locally advancedDistant metastasis
Pain 20 Pain gt20
MaleFemale
Age lt65Age 65
United StatesCanada
Rest of World
HER1EGFR positiveHER1EGFR negative
HER1EGFR unknown
1
082 07-10 569
087 07-11 463056 04-08 106
094 06-14 138078 06-09 431
070 05-09 258098 08-13 296
074 06-09 298096 07-13 271
074 06-10 301093 07-12 268
071 05-09 211079 05-12 117096 07-13 241
073 04-12 74077 05-13 71086 07-11 424
Fact
ors
Moore et al JCO 2007
ADVANCED DISEASE
Events
Tarceva () n=282
Placebo () n=280
Any Grade 34 Any Grade 34Rash 72 6 29 1Diarrhoea 56 6 41 2Infection 43 17 34 16Stomatitis 23 lt1 14 0Pneumonitis 2 2 1 lt1Fatigue 89 15 86 15
PA3 studyPA3 study Adverse eventsAdverse events
Moore et al JCO 2007
ADVANCED DISEASE
AccetableAccetable standard standard systemicsystemic treatmenttreatment options 2009options 2009
bullbull GEM GEM alonealonebullbull GEMGEM--erlotiniberlotinib
ndashndash registredregistred for for metastaticmetastatic PC PC onlyonly mOSmOS + 12 + 12 daysdays somesome additionaladditional toxicitytoxicity
bullbull GEMGEM--CAP CAP mOSmOS + 1 + 1 monthmonth onlyonly significantsignificant in in metameta--analysisanalysis
bullbull GEMGEM--platinumplatinum ndashndash doubtfuldoubtful effecteffect -- nownow not not significantsignificant in in metameta--
analysisanalysis significantsignificant toxicitytoxicity
ADVANCED DISEASE
SUPPORTIVE CARESUPPORTIVE CARE
Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer
SUPPORTIVE CARE
GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)
enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009
Baggrund
VTE forekommer hos ca 10 af patienter med PC
Formaringl
Undersoslashge effekt af LMWH (Klexane) i kombination med
kemoterapi mht frekvens af VTE og mOS
Inklusion
Avanceret PC ikke tidligere kemoterapi
Karnofsky
PS gt 60
Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor
2 aringr
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al ASCO 2009
Antal af VTE 15152 i observation ndash 2160 i LMWH
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al
Konklusion
LMWH er effektiv og sikker behandling til forebyggelse af
VTE hos patienter med pancreascancer
Endelige resultater paring
mOS og mTTP
afventes
SUPPORTIVE CARE
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
GemcitabineGemcitabine vs 5vs 5--FUFU
Burris H et al J Clin Oncol 1997152403-2413
Gemcitabine 5-FU P
Clinical benefit response 24 5 0002 Median survival (months) 57 44 0002 Time to progression (months) 21 09 0001 6-month survival 46 31 1-year survival 18 2 Partial response 54 0 Stable disease 393 19 Composite of measurements of pain (analgesic consumption and pain intensity) Karnofsky
performance status and weight
ADVANCED DISEASE
SurvivalSurvival of of GemGem--treatedtreated patients patients accordingaccording to performance statusto performance status
Storinolo et al Cancer 1998
ADVANCED DISEASE
Combination chemotherapyCombination chemotherapy GemGem--CapCap
JCO october 2009
ADVANCED DISEASE
CunninghamCunningham et al GEMet al GEM--CAPCAP
Hazard ratio 080 95 CI 065ndash098Log-rank p=0026
Eur J Cancer Suppl 2005
Interim analysis 2005Final analysis 2009
ADVANCED DISEASE
MetaMeta--analysisanalysis of GEMof GEM--CAPCAP
Cunningham et al JCO 2009
ADVANCED DISEASE
Gem vs Gem vs GemGem‐‐platinumplatinumDi Miao A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
ASCO 2009
Gemcitabin
som kontrol +
cisplatin
ugentlig 25mgm2N=201
Gemcitabin
ugentlig i 7 uger
2 ugers pause og dag 18 15 i
4 ugers cyklusN=199
400 pt
ADVANCED DISEASE
GemGem GemCisGemCis
OSOS11‐‐year year survivalsurvivalPFSPFS
AnAnaeligaeligmimiTrombocytopeniTrombocytopeni
83 mdr 83 mdr 340 340 39 mdr 39 mdr
39392929
72 mdr 72 mdr 307 307 38 mdr38 mdr
50505757
A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma
The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
Di Miao
bull Alle endepunkter insignifikantebull Subgruppeanalyse
af PS 0 Signifikant negativ effekt
bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant
efter inklusion af dette studium
ADVANCED DISEASE
CombinationCombination chemotherapychemotherapy and and effecteffect accordingaccording to to performance statusperformance status
Heinemann et al BMC Cancer 2008
ADVANCED DISEASE
PA3 study GemPA3 study Gem--erlotiniberlotinib Overall survivalOverall survival
10090807060504030201
0
Surv
ival
pro
babi
lity
0 6 12 18 24Survival (months)
Tarcevatrade gemcitabine
(n=285)
Placebo gemcitabine
(n=284)
Median survival (months) 637 591
1-year survival 24 17
HR=079 (95 CI 066-095) P=0011 (adjusted for PS and extent of disease at randomization)
TarcevaTM + gemcitabinePlacebo + gemcitabine
Moore et al JCO 2007
ADVANCED DISEASE
PA3 studyPA3 study Hazard ratios for survivalHazard ratios for survival
HR 95 CI n
Tarcevaplacebo
Performance status 0-1Performance status 2
Locally advancedDistant metastasis
Pain 20 Pain gt20
MaleFemale
Age lt65Age 65
United StatesCanada
Rest of World
HER1EGFR positiveHER1EGFR negative
HER1EGFR unknown
1
082 07-10 569
087 07-11 463056 04-08 106
094 06-14 138078 06-09 431
070 05-09 258098 08-13 296
074 06-09 298096 07-13 271
074 06-10 301093 07-12 268
071 05-09 211079 05-12 117096 07-13 241
073 04-12 74077 05-13 71086 07-11 424
Fact
ors
Moore et al JCO 2007
ADVANCED DISEASE
Events
Tarceva () n=282
Placebo () n=280
Any Grade 34 Any Grade 34Rash 72 6 29 1Diarrhoea 56 6 41 2Infection 43 17 34 16Stomatitis 23 lt1 14 0Pneumonitis 2 2 1 lt1Fatigue 89 15 86 15
PA3 studyPA3 study Adverse eventsAdverse events
Moore et al JCO 2007
ADVANCED DISEASE
AccetableAccetable standard standard systemicsystemic treatmenttreatment options 2009options 2009
bullbull GEM GEM alonealonebullbull GEMGEM--erlotiniberlotinib
ndashndash registredregistred for for metastaticmetastatic PC PC onlyonly mOSmOS + 12 + 12 daysdays somesome additionaladditional toxicitytoxicity
bullbull GEMGEM--CAP CAP mOSmOS + 1 + 1 monthmonth onlyonly significantsignificant in in metameta--analysisanalysis
bullbull GEMGEM--platinumplatinum ndashndash doubtfuldoubtful effecteffect -- nownow not not significantsignificant in in metameta--
analysisanalysis significantsignificant toxicitytoxicity
ADVANCED DISEASE
SUPPORTIVE CARESUPPORTIVE CARE
Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer
SUPPORTIVE CARE
GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)
enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009
Baggrund
VTE forekommer hos ca 10 af patienter med PC
Formaringl
Undersoslashge effekt af LMWH (Klexane) i kombination med
kemoterapi mht frekvens af VTE og mOS
Inklusion
Avanceret PC ikke tidligere kemoterapi
Karnofsky
PS gt 60
Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor
2 aringr
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al ASCO 2009
Antal af VTE 15152 i observation ndash 2160 i LMWH
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al
Konklusion
LMWH er effektiv og sikker behandling til forebyggelse af
VTE hos patienter med pancreascancer
Endelige resultater paring
mOS og mTTP
afventes
SUPPORTIVE CARE
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
SurvivalSurvival of of GemGem--treatedtreated patients patients accordingaccording to performance statusto performance status
Storinolo et al Cancer 1998
ADVANCED DISEASE
Combination chemotherapyCombination chemotherapy GemGem--CapCap
JCO october 2009
ADVANCED DISEASE
CunninghamCunningham et al GEMet al GEM--CAPCAP
Hazard ratio 080 95 CI 065ndash098Log-rank p=0026
Eur J Cancer Suppl 2005
Interim analysis 2005Final analysis 2009
ADVANCED DISEASE
MetaMeta--analysisanalysis of GEMof GEM--CAPCAP
Cunningham et al JCO 2009
ADVANCED DISEASE
Gem vs Gem vs GemGem‐‐platinumplatinumDi Miao A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
ASCO 2009
Gemcitabin
som kontrol +
cisplatin
ugentlig 25mgm2N=201
Gemcitabin
ugentlig i 7 uger
2 ugers pause og dag 18 15 i
4 ugers cyklusN=199
400 pt
ADVANCED DISEASE
GemGem GemCisGemCis
OSOS11‐‐year year survivalsurvivalPFSPFS
AnAnaeligaeligmimiTrombocytopeniTrombocytopeni
83 mdr 83 mdr 340 340 39 mdr 39 mdr
39392929
72 mdr 72 mdr 307 307 38 mdr38 mdr
50505757
A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma
The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
Di Miao
bull Alle endepunkter insignifikantebull Subgruppeanalyse
af PS 0 Signifikant negativ effekt
bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant
efter inklusion af dette studium
ADVANCED DISEASE
CombinationCombination chemotherapychemotherapy and and effecteffect accordingaccording to to performance statusperformance status
Heinemann et al BMC Cancer 2008
ADVANCED DISEASE
PA3 study GemPA3 study Gem--erlotiniberlotinib Overall survivalOverall survival
10090807060504030201
0
Surv
ival
pro
babi
lity
0 6 12 18 24Survival (months)
Tarcevatrade gemcitabine
(n=285)
Placebo gemcitabine
(n=284)
Median survival (months) 637 591
1-year survival 24 17
HR=079 (95 CI 066-095) P=0011 (adjusted for PS and extent of disease at randomization)
TarcevaTM + gemcitabinePlacebo + gemcitabine
Moore et al JCO 2007
ADVANCED DISEASE
PA3 studyPA3 study Hazard ratios for survivalHazard ratios for survival
HR 95 CI n
Tarcevaplacebo
Performance status 0-1Performance status 2
Locally advancedDistant metastasis
Pain 20 Pain gt20
MaleFemale
Age lt65Age 65
United StatesCanada
Rest of World
HER1EGFR positiveHER1EGFR negative
HER1EGFR unknown
1
082 07-10 569
087 07-11 463056 04-08 106
094 06-14 138078 06-09 431
070 05-09 258098 08-13 296
074 06-09 298096 07-13 271
074 06-10 301093 07-12 268
071 05-09 211079 05-12 117096 07-13 241
073 04-12 74077 05-13 71086 07-11 424
Fact
ors
Moore et al JCO 2007
ADVANCED DISEASE
Events
Tarceva () n=282
Placebo () n=280
Any Grade 34 Any Grade 34Rash 72 6 29 1Diarrhoea 56 6 41 2Infection 43 17 34 16Stomatitis 23 lt1 14 0Pneumonitis 2 2 1 lt1Fatigue 89 15 86 15
PA3 studyPA3 study Adverse eventsAdverse events
Moore et al JCO 2007
ADVANCED DISEASE
AccetableAccetable standard standard systemicsystemic treatmenttreatment options 2009options 2009
bullbull GEM GEM alonealonebullbull GEMGEM--erlotiniberlotinib
ndashndash registredregistred for for metastaticmetastatic PC PC onlyonly mOSmOS + 12 + 12 daysdays somesome additionaladditional toxicitytoxicity
bullbull GEMGEM--CAP CAP mOSmOS + 1 + 1 monthmonth onlyonly significantsignificant in in metameta--analysisanalysis
bullbull GEMGEM--platinumplatinum ndashndash doubtfuldoubtful effecteffect -- nownow not not significantsignificant in in metameta--
analysisanalysis significantsignificant toxicitytoxicity
ADVANCED DISEASE
SUPPORTIVE CARESUPPORTIVE CARE
Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer
SUPPORTIVE CARE
GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)
enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009
Baggrund
VTE forekommer hos ca 10 af patienter med PC
Formaringl
Undersoslashge effekt af LMWH (Klexane) i kombination med
kemoterapi mht frekvens af VTE og mOS
Inklusion
Avanceret PC ikke tidligere kemoterapi
Karnofsky
PS gt 60
Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor
2 aringr
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al ASCO 2009
Antal af VTE 15152 i observation ndash 2160 i LMWH
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al
Konklusion
LMWH er effektiv og sikker behandling til forebyggelse af
VTE hos patienter med pancreascancer
Endelige resultater paring
mOS og mTTP
afventes
SUPPORTIVE CARE
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
Combination chemotherapyCombination chemotherapy GemGem--CapCap
JCO october 2009
ADVANCED DISEASE
CunninghamCunningham et al GEMet al GEM--CAPCAP
Hazard ratio 080 95 CI 065ndash098Log-rank p=0026
Eur J Cancer Suppl 2005
Interim analysis 2005Final analysis 2009
ADVANCED DISEASE
MetaMeta--analysisanalysis of GEMof GEM--CAPCAP
Cunningham et al JCO 2009
ADVANCED DISEASE
Gem vs Gem vs GemGem‐‐platinumplatinumDi Miao A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
ASCO 2009
Gemcitabin
som kontrol +
cisplatin
ugentlig 25mgm2N=201
Gemcitabin
ugentlig i 7 uger
2 ugers pause og dag 18 15 i
4 ugers cyklusN=199
400 pt
ADVANCED DISEASE
GemGem GemCisGemCis
OSOS11‐‐year year survivalsurvivalPFSPFS
AnAnaeligaeligmimiTrombocytopeniTrombocytopeni
83 mdr 83 mdr 340 340 39 mdr 39 mdr
39392929
72 mdr 72 mdr 307 307 38 mdr38 mdr
50505757
A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma
The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
Di Miao
bull Alle endepunkter insignifikantebull Subgruppeanalyse
af PS 0 Signifikant negativ effekt
bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant
efter inklusion af dette studium
ADVANCED DISEASE
CombinationCombination chemotherapychemotherapy and and effecteffect accordingaccording to to performance statusperformance status
Heinemann et al BMC Cancer 2008
ADVANCED DISEASE
PA3 study GemPA3 study Gem--erlotiniberlotinib Overall survivalOverall survival
10090807060504030201
0
Surv
ival
pro
babi
lity
0 6 12 18 24Survival (months)
Tarcevatrade gemcitabine
(n=285)
Placebo gemcitabine
(n=284)
Median survival (months) 637 591
1-year survival 24 17
HR=079 (95 CI 066-095) P=0011 (adjusted for PS and extent of disease at randomization)
TarcevaTM + gemcitabinePlacebo + gemcitabine
Moore et al JCO 2007
ADVANCED DISEASE
PA3 studyPA3 study Hazard ratios for survivalHazard ratios for survival
HR 95 CI n
Tarcevaplacebo
Performance status 0-1Performance status 2
Locally advancedDistant metastasis
Pain 20 Pain gt20
MaleFemale
Age lt65Age 65
United StatesCanada
Rest of World
HER1EGFR positiveHER1EGFR negative
HER1EGFR unknown
1
082 07-10 569
087 07-11 463056 04-08 106
094 06-14 138078 06-09 431
070 05-09 258098 08-13 296
074 06-09 298096 07-13 271
074 06-10 301093 07-12 268
071 05-09 211079 05-12 117096 07-13 241
073 04-12 74077 05-13 71086 07-11 424
Fact
ors
Moore et al JCO 2007
ADVANCED DISEASE
Events
Tarceva () n=282
Placebo () n=280
Any Grade 34 Any Grade 34Rash 72 6 29 1Diarrhoea 56 6 41 2Infection 43 17 34 16Stomatitis 23 lt1 14 0Pneumonitis 2 2 1 lt1Fatigue 89 15 86 15
PA3 studyPA3 study Adverse eventsAdverse events
Moore et al JCO 2007
ADVANCED DISEASE
AccetableAccetable standard standard systemicsystemic treatmenttreatment options 2009options 2009
bullbull GEM GEM alonealonebullbull GEMGEM--erlotiniberlotinib
ndashndash registredregistred for for metastaticmetastatic PC PC onlyonly mOSmOS + 12 + 12 daysdays somesome additionaladditional toxicitytoxicity
bullbull GEMGEM--CAP CAP mOSmOS + 1 + 1 monthmonth onlyonly significantsignificant in in metameta--analysisanalysis
bullbull GEMGEM--platinumplatinum ndashndash doubtfuldoubtful effecteffect -- nownow not not significantsignificant in in metameta--
analysisanalysis significantsignificant toxicitytoxicity
ADVANCED DISEASE
SUPPORTIVE CARESUPPORTIVE CARE
Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer
SUPPORTIVE CARE
GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)
enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009
Baggrund
VTE forekommer hos ca 10 af patienter med PC
Formaringl
Undersoslashge effekt af LMWH (Klexane) i kombination med
kemoterapi mht frekvens af VTE og mOS
Inklusion
Avanceret PC ikke tidligere kemoterapi
Karnofsky
PS gt 60
Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor
2 aringr
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al ASCO 2009
Antal af VTE 15152 i observation ndash 2160 i LMWH
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al
Konklusion
LMWH er effektiv og sikker behandling til forebyggelse af
VTE hos patienter med pancreascancer
Endelige resultater paring
mOS og mTTP
afventes
SUPPORTIVE CARE
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
CunninghamCunningham et al GEMet al GEM--CAPCAP
Hazard ratio 080 95 CI 065ndash098Log-rank p=0026
Eur J Cancer Suppl 2005
Interim analysis 2005Final analysis 2009
ADVANCED DISEASE
MetaMeta--analysisanalysis of GEMof GEM--CAPCAP
Cunningham et al JCO 2009
ADVANCED DISEASE
Gem vs Gem vs GemGem‐‐platinumplatinumDi Miao A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
ASCO 2009
Gemcitabin
som kontrol +
cisplatin
ugentlig 25mgm2N=201
Gemcitabin
ugentlig i 7 uger
2 ugers pause og dag 18 15 i
4 ugers cyklusN=199
400 pt
ADVANCED DISEASE
GemGem GemCisGemCis
OSOS11‐‐year year survivalsurvivalPFSPFS
AnAnaeligaeligmimiTrombocytopeniTrombocytopeni
83 mdr 83 mdr 340 340 39 mdr 39 mdr
39392929
72 mdr 72 mdr 307 307 38 mdr38 mdr
50505757
A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma
The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
Di Miao
bull Alle endepunkter insignifikantebull Subgruppeanalyse
af PS 0 Signifikant negativ effekt
bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant
efter inklusion af dette studium
ADVANCED DISEASE
CombinationCombination chemotherapychemotherapy and and effecteffect accordingaccording to to performance statusperformance status
Heinemann et al BMC Cancer 2008
ADVANCED DISEASE
PA3 study GemPA3 study Gem--erlotiniberlotinib Overall survivalOverall survival
10090807060504030201
0
Surv
ival
pro
babi
lity
0 6 12 18 24Survival (months)
Tarcevatrade gemcitabine
(n=285)
Placebo gemcitabine
(n=284)
Median survival (months) 637 591
1-year survival 24 17
HR=079 (95 CI 066-095) P=0011 (adjusted for PS and extent of disease at randomization)
TarcevaTM + gemcitabinePlacebo + gemcitabine
Moore et al JCO 2007
ADVANCED DISEASE
PA3 studyPA3 study Hazard ratios for survivalHazard ratios for survival
HR 95 CI n
Tarcevaplacebo
Performance status 0-1Performance status 2
Locally advancedDistant metastasis
Pain 20 Pain gt20
MaleFemale
Age lt65Age 65
United StatesCanada
Rest of World
HER1EGFR positiveHER1EGFR negative
HER1EGFR unknown
1
082 07-10 569
087 07-11 463056 04-08 106
094 06-14 138078 06-09 431
070 05-09 258098 08-13 296
074 06-09 298096 07-13 271
074 06-10 301093 07-12 268
071 05-09 211079 05-12 117096 07-13 241
073 04-12 74077 05-13 71086 07-11 424
Fact
ors
Moore et al JCO 2007
ADVANCED DISEASE
Events
Tarceva () n=282
Placebo () n=280
Any Grade 34 Any Grade 34Rash 72 6 29 1Diarrhoea 56 6 41 2Infection 43 17 34 16Stomatitis 23 lt1 14 0Pneumonitis 2 2 1 lt1Fatigue 89 15 86 15
PA3 studyPA3 study Adverse eventsAdverse events
Moore et al JCO 2007
ADVANCED DISEASE
AccetableAccetable standard standard systemicsystemic treatmenttreatment options 2009options 2009
bullbull GEM GEM alonealonebullbull GEMGEM--erlotiniberlotinib
ndashndash registredregistred for for metastaticmetastatic PC PC onlyonly mOSmOS + 12 + 12 daysdays somesome additionaladditional toxicitytoxicity
bullbull GEMGEM--CAP CAP mOSmOS + 1 + 1 monthmonth onlyonly significantsignificant in in metameta--analysisanalysis
bullbull GEMGEM--platinumplatinum ndashndash doubtfuldoubtful effecteffect -- nownow not not significantsignificant in in metameta--
analysisanalysis significantsignificant toxicitytoxicity
ADVANCED DISEASE
SUPPORTIVE CARESUPPORTIVE CARE
Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer
SUPPORTIVE CARE
GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)
enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009
Baggrund
VTE forekommer hos ca 10 af patienter med PC
Formaringl
Undersoslashge effekt af LMWH (Klexane) i kombination med
kemoterapi mht frekvens af VTE og mOS
Inklusion
Avanceret PC ikke tidligere kemoterapi
Karnofsky
PS gt 60
Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor
2 aringr
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al ASCO 2009
Antal af VTE 15152 i observation ndash 2160 i LMWH
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al
Konklusion
LMWH er effektiv og sikker behandling til forebyggelse af
VTE hos patienter med pancreascancer
Endelige resultater paring
mOS og mTTP
afventes
SUPPORTIVE CARE
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
MetaMeta--analysisanalysis of GEMof GEM--CAPCAP
Cunningham et al JCO 2009
ADVANCED DISEASE
Gem vs Gem vs GemGem‐‐platinumplatinumDi Miao A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
ASCO 2009
Gemcitabin
som kontrol +
cisplatin
ugentlig 25mgm2N=201
Gemcitabin
ugentlig i 7 uger
2 ugers pause og dag 18 15 i
4 ugers cyklusN=199
400 pt
ADVANCED DISEASE
GemGem GemCisGemCis
OSOS11‐‐year year survivalsurvivalPFSPFS
AnAnaeligaeligmimiTrombocytopeniTrombocytopeni
83 mdr 83 mdr 340 340 39 mdr 39 mdr
39392929
72 mdr 72 mdr 307 307 38 mdr38 mdr
50505757
A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma
The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
Di Miao
bull Alle endepunkter insignifikantebull Subgruppeanalyse
af PS 0 Signifikant negativ effekt
bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant
efter inklusion af dette studium
ADVANCED DISEASE
CombinationCombination chemotherapychemotherapy and and effecteffect accordingaccording to to performance statusperformance status
Heinemann et al BMC Cancer 2008
ADVANCED DISEASE
PA3 study GemPA3 study Gem--erlotiniberlotinib Overall survivalOverall survival
10090807060504030201
0
Surv
ival
pro
babi
lity
0 6 12 18 24Survival (months)
Tarcevatrade gemcitabine
(n=285)
Placebo gemcitabine
(n=284)
Median survival (months) 637 591
1-year survival 24 17
HR=079 (95 CI 066-095) P=0011 (adjusted for PS and extent of disease at randomization)
TarcevaTM + gemcitabinePlacebo + gemcitabine
Moore et al JCO 2007
ADVANCED DISEASE
PA3 studyPA3 study Hazard ratios for survivalHazard ratios for survival
HR 95 CI n
Tarcevaplacebo
Performance status 0-1Performance status 2
Locally advancedDistant metastasis
Pain 20 Pain gt20
MaleFemale
Age lt65Age 65
United StatesCanada
Rest of World
HER1EGFR positiveHER1EGFR negative
HER1EGFR unknown
1
082 07-10 569
087 07-11 463056 04-08 106
094 06-14 138078 06-09 431
070 05-09 258098 08-13 296
074 06-09 298096 07-13 271
074 06-10 301093 07-12 268
071 05-09 211079 05-12 117096 07-13 241
073 04-12 74077 05-13 71086 07-11 424
Fact
ors
Moore et al JCO 2007
ADVANCED DISEASE
Events
Tarceva () n=282
Placebo () n=280
Any Grade 34 Any Grade 34Rash 72 6 29 1Diarrhoea 56 6 41 2Infection 43 17 34 16Stomatitis 23 lt1 14 0Pneumonitis 2 2 1 lt1Fatigue 89 15 86 15
PA3 studyPA3 study Adverse eventsAdverse events
Moore et al JCO 2007
ADVANCED DISEASE
AccetableAccetable standard standard systemicsystemic treatmenttreatment options 2009options 2009
bullbull GEM GEM alonealonebullbull GEMGEM--erlotiniberlotinib
ndashndash registredregistred for for metastaticmetastatic PC PC onlyonly mOSmOS + 12 + 12 daysdays somesome additionaladditional toxicitytoxicity
bullbull GEMGEM--CAP CAP mOSmOS + 1 + 1 monthmonth onlyonly significantsignificant in in metameta--analysisanalysis
bullbull GEMGEM--platinumplatinum ndashndash doubtfuldoubtful effecteffect -- nownow not not significantsignificant in in metameta--
analysisanalysis significantsignificant toxicitytoxicity
ADVANCED DISEASE
SUPPORTIVE CARESUPPORTIVE CARE
Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer
SUPPORTIVE CARE
GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)
enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009
Baggrund
VTE forekommer hos ca 10 af patienter med PC
Formaringl
Undersoslashge effekt af LMWH (Klexane) i kombination med
kemoterapi mht frekvens af VTE og mOS
Inklusion
Avanceret PC ikke tidligere kemoterapi
Karnofsky
PS gt 60
Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor
2 aringr
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al ASCO 2009
Antal af VTE 15152 i observation ndash 2160 i LMWH
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al
Konklusion
LMWH er effektiv og sikker behandling til forebyggelse af
VTE hos patienter med pancreascancer
Endelige resultater paring
mOS og mTTP
afventes
SUPPORTIVE CARE
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
Gem vs Gem vs GemGem‐‐platinumplatinumDi Miao A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
ASCO 2009
Gemcitabin
som kontrol +
cisplatin
ugentlig 25mgm2N=201
Gemcitabin
ugentlig i 7 uger
2 ugers pause og dag 18 15 i
4 ugers cyklusN=199
400 pt
ADVANCED DISEASE
GemGem GemCisGemCis
OSOS11‐‐year year survivalsurvivalPFSPFS
AnAnaeligaeligmimiTrombocytopeniTrombocytopeni
83 mdr 83 mdr 340 340 39 mdr 39 mdr
39392929
72 mdr 72 mdr 307 307 38 mdr38 mdr
50505757
A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma
The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
Di Miao
bull Alle endepunkter insignifikantebull Subgruppeanalyse
af PS 0 Signifikant negativ effekt
bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant
efter inklusion af dette studium
ADVANCED DISEASE
CombinationCombination chemotherapychemotherapy and and effecteffect accordingaccording to to performance statusperformance status
Heinemann et al BMC Cancer 2008
ADVANCED DISEASE
PA3 study GemPA3 study Gem--erlotiniberlotinib Overall survivalOverall survival
10090807060504030201
0
Surv
ival
pro
babi
lity
0 6 12 18 24Survival (months)
Tarcevatrade gemcitabine
(n=285)
Placebo gemcitabine
(n=284)
Median survival (months) 637 591
1-year survival 24 17
HR=079 (95 CI 066-095) P=0011 (adjusted for PS and extent of disease at randomization)
TarcevaTM + gemcitabinePlacebo + gemcitabine
Moore et al JCO 2007
ADVANCED DISEASE
PA3 studyPA3 study Hazard ratios for survivalHazard ratios for survival
HR 95 CI n
Tarcevaplacebo
Performance status 0-1Performance status 2
Locally advancedDistant metastasis
Pain 20 Pain gt20
MaleFemale
Age lt65Age 65
United StatesCanada
Rest of World
HER1EGFR positiveHER1EGFR negative
HER1EGFR unknown
1
082 07-10 569
087 07-11 463056 04-08 106
094 06-14 138078 06-09 431
070 05-09 258098 08-13 296
074 06-09 298096 07-13 271
074 06-10 301093 07-12 268
071 05-09 211079 05-12 117096 07-13 241
073 04-12 74077 05-13 71086 07-11 424
Fact
ors
Moore et al JCO 2007
ADVANCED DISEASE
Events
Tarceva () n=282
Placebo () n=280
Any Grade 34 Any Grade 34Rash 72 6 29 1Diarrhoea 56 6 41 2Infection 43 17 34 16Stomatitis 23 lt1 14 0Pneumonitis 2 2 1 lt1Fatigue 89 15 86 15
PA3 studyPA3 study Adverse eventsAdverse events
Moore et al JCO 2007
ADVANCED DISEASE
AccetableAccetable standard standard systemicsystemic treatmenttreatment options 2009options 2009
bullbull GEM GEM alonealonebullbull GEMGEM--erlotiniberlotinib
ndashndash registredregistred for for metastaticmetastatic PC PC onlyonly mOSmOS + 12 + 12 daysdays somesome additionaladditional toxicitytoxicity
bullbull GEMGEM--CAP CAP mOSmOS + 1 + 1 monthmonth onlyonly significantsignificant in in metameta--analysisanalysis
bullbull GEMGEM--platinumplatinum ndashndash doubtfuldoubtful effecteffect -- nownow not not significantsignificant in in metameta--
analysisanalysis significantsignificant toxicitytoxicity
ADVANCED DISEASE
SUPPORTIVE CARESUPPORTIVE CARE
Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer
SUPPORTIVE CARE
GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)
enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009
Baggrund
VTE forekommer hos ca 10 af patienter med PC
Formaringl
Undersoslashge effekt af LMWH (Klexane) i kombination med
kemoterapi mht frekvens af VTE og mOS
Inklusion
Avanceret PC ikke tidligere kemoterapi
Karnofsky
PS gt 60
Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor
2 aringr
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al ASCO 2009
Antal af VTE 15152 i observation ndash 2160 i LMWH
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al
Konklusion
LMWH er effektiv og sikker behandling til forebyggelse af
VTE hos patienter med pancreascancer
Endelige resultater paring
mOS og mTTP
afventes
SUPPORTIVE CARE
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
GemGem GemCisGemCis
OSOS11‐‐year year survivalsurvivalPFSPFS
AnAnaeligaeligmimiTrombocytopeniTrombocytopeni
83 mdr 83 mdr 340 340 39 mdr 39 mdr
39392929
72 mdr 72 mdr 307 307 38 mdr38 mdr
50505757
A randomized
trial
of gemcitabine
(G) versus G plus cisplatin
in chemotherapy‐naive
advanced
pancreatic
adenocarcinoma
The GIP‐1 (Gruppo
Italiano Pancreasmdash
GOIMGISCADGOIRC)
study
Di Miao
bull Alle endepunkter insignifikantebull Subgruppeanalyse
af PS 0 Signifikant negativ effekt
bull Tidligere meta‐analyse som viste effekt af Gem‐platin‐kombinationer nu insignifikant
efter inklusion af dette studium
ADVANCED DISEASE
CombinationCombination chemotherapychemotherapy and and effecteffect accordingaccording to to performance statusperformance status
Heinemann et al BMC Cancer 2008
ADVANCED DISEASE
PA3 study GemPA3 study Gem--erlotiniberlotinib Overall survivalOverall survival
10090807060504030201
0
Surv
ival
pro
babi
lity
0 6 12 18 24Survival (months)
Tarcevatrade gemcitabine
(n=285)
Placebo gemcitabine
(n=284)
Median survival (months) 637 591
1-year survival 24 17
HR=079 (95 CI 066-095) P=0011 (adjusted for PS and extent of disease at randomization)
TarcevaTM + gemcitabinePlacebo + gemcitabine
Moore et al JCO 2007
ADVANCED DISEASE
PA3 studyPA3 study Hazard ratios for survivalHazard ratios for survival
HR 95 CI n
Tarcevaplacebo
Performance status 0-1Performance status 2
Locally advancedDistant metastasis
Pain 20 Pain gt20
MaleFemale
Age lt65Age 65
United StatesCanada
Rest of World
HER1EGFR positiveHER1EGFR negative
HER1EGFR unknown
1
082 07-10 569
087 07-11 463056 04-08 106
094 06-14 138078 06-09 431
070 05-09 258098 08-13 296
074 06-09 298096 07-13 271
074 06-10 301093 07-12 268
071 05-09 211079 05-12 117096 07-13 241
073 04-12 74077 05-13 71086 07-11 424
Fact
ors
Moore et al JCO 2007
ADVANCED DISEASE
Events
Tarceva () n=282
Placebo () n=280
Any Grade 34 Any Grade 34Rash 72 6 29 1Diarrhoea 56 6 41 2Infection 43 17 34 16Stomatitis 23 lt1 14 0Pneumonitis 2 2 1 lt1Fatigue 89 15 86 15
PA3 studyPA3 study Adverse eventsAdverse events
Moore et al JCO 2007
ADVANCED DISEASE
AccetableAccetable standard standard systemicsystemic treatmenttreatment options 2009options 2009
bullbull GEM GEM alonealonebullbull GEMGEM--erlotiniberlotinib
ndashndash registredregistred for for metastaticmetastatic PC PC onlyonly mOSmOS + 12 + 12 daysdays somesome additionaladditional toxicitytoxicity
bullbull GEMGEM--CAP CAP mOSmOS + 1 + 1 monthmonth onlyonly significantsignificant in in metameta--analysisanalysis
bullbull GEMGEM--platinumplatinum ndashndash doubtfuldoubtful effecteffect -- nownow not not significantsignificant in in metameta--
analysisanalysis significantsignificant toxicitytoxicity
ADVANCED DISEASE
SUPPORTIVE CARESUPPORTIVE CARE
Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer
SUPPORTIVE CARE
GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)
enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009
Baggrund
VTE forekommer hos ca 10 af patienter med PC
Formaringl
Undersoslashge effekt af LMWH (Klexane) i kombination med
kemoterapi mht frekvens af VTE og mOS
Inklusion
Avanceret PC ikke tidligere kemoterapi
Karnofsky
PS gt 60
Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor
2 aringr
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al ASCO 2009
Antal af VTE 15152 i observation ndash 2160 i LMWH
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al
Konklusion
LMWH er effektiv og sikker behandling til forebyggelse af
VTE hos patienter med pancreascancer
Endelige resultater paring
mOS og mTTP
afventes
SUPPORTIVE CARE
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
CombinationCombination chemotherapychemotherapy and and effecteffect accordingaccording to to performance statusperformance status
Heinemann et al BMC Cancer 2008
ADVANCED DISEASE
PA3 study GemPA3 study Gem--erlotiniberlotinib Overall survivalOverall survival
10090807060504030201
0
Surv
ival
pro
babi
lity
0 6 12 18 24Survival (months)
Tarcevatrade gemcitabine
(n=285)
Placebo gemcitabine
(n=284)
Median survival (months) 637 591
1-year survival 24 17
HR=079 (95 CI 066-095) P=0011 (adjusted for PS and extent of disease at randomization)
TarcevaTM + gemcitabinePlacebo + gemcitabine
Moore et al JCO 2007
ADVANCED DISEASE
PA3 studyPA3 study Hazard ratios for survivalHazard ratios for survival
HR 95 CI n
Tarcevaplacebo
Performance status 0-1Performance status 2
Locally advancedDistant metastasis
Pain 20 Pain gt20
MaleFemale
Age lt65Age 65
United StatesCanada
Rest of World
HER1EGFR positiveHER1EGFR negative
HER1EGFR unknown
1
082 07-10 569
087 07-11 463056 04-08 106
094 06-14 138078 06-09 431
070 05-09 258098 08-13 296
074 06-09 298096 07-13 271
074 06-10 301093 07-12 268
071 05-09 211079 05-12 117096 07-13 241
073 04-12 74077 05-13 71086 07-11 424
Fact
ors
Moore et al JCO 2007
ADVANCED DISEASE
Events
Tarceva () n=282
Placebo () n=280
Any Grade 34 Any Grade 34Rash 72 6 29 1Diarrhoea 56 6 41 2Infection 43 17 34 16Stomatitis 23 lt1 14 0Pneumonitis 2 2 1 lt1Fatigue 89 15 86 15
PA3 studyPA3 study Adverse eventsAdverse events
Moore et al JCO 2007
ADVANCED DISEASE
AccetableAccetable standard standard systemicsystemic treatmenttreatment options 2009options 2009
bullbull GEM GEM alonealonebullbull GEMGEM--erlotiniberlotinib
ndashndash registredregistred for for metastaticmetastatic PC PC onlyonly mOSmOS + 12 + 12 daysdays somesome additionaladditional toxicitytoxicity
bullbull GEMGEM--CAP CAP mOSmOS + 1 + 1 monthmonth onlyonly significantsignificant in in metameta--analysisanalysis
bullbull GEMGEM--platinumplatinum ndashndash doubtfuldoubtful effecteffect -- nownow not not significantsignificant in in metameta--
analysisanalysis significantsignificant toxicitytoxicity
ADVANCED DISEASE
SUPPORTIVE CARESUPPORTIVE CARE
Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer
SUPPORTIVE CARE
GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)
enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009
Baggrund
VTE forekommer hos ca 10 af patienter med PC
Formaringl
Undersoslashge effekt af LMWH (Klexane) i kombination med
kemoterapi mht frekvens af VTE og mOS
Inklusion
Avanceret PC ikke tidligere kemoterapi
Karnofsky
PS gt 60
Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor
2 aringr
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al ASCO 2009
Antal af VTE 15152 i observation ndash 2160 i LMWH
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al
Konklusion
LMWH er effektiv og sikker behandling til forebyggelse af
VTE hos patienter med pancreascancer
Endelige resultater paring
mOS og mTTP
afventes
SUPPORTIVE CARE
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
PA3 study GemPA3 study Gem--erlotiniberlotinib Overall survivalOverall survival
10090807060504030201
0
Surv
ival
pro
babi
lity
0 6 12 18 24Survival (months)
Tarcevatrade gemcitabine
(n=285)
Placebo gemcitabine
(n=284)
Median survival (months) 637 591
1-year survival 24 17
HR=079 (95 CI 066-095) P=0011 (adjusted for PS and extent of disease at randomization)
TarcevaTM + gemcitabinePlacebo + gemcitabine
Moore et al JCO 2007
ADVANCED DISEASE
PA3 studyPA3 study Hazard ratios for survivalHazard ratios for survival
HR 95 CI n
Tarcevaplacebo
Performance status 0-1Performance status 2
Locally advancedDistant metastasis
Pain 20 Pain gt20
MaleFemale
Age lt65Age 65
United StatesCanada
Rest of World
HER1EGFR positiveHER1EGFR negative
HER1EGFR unknown
1
082 07-10 569
087 07-11 463056 04-08 106
094 06-14 138078 06-09 431
070 05-09 258098 08-13 296
074 06-09 298096 07-13 271
074 06-10 301093 07-12 268
071 05-09 211079 05-12 117096 07-13 241
073 04-12 74077 05-13 71086 07-11 424
Fact
ors
Moore et al JCO 2007
ADVANCED DISEASE
Events
Tarceva () n=282
Placebo () n=280
Any Grade 34 Any Grade 34Rash 72 6 29 1Diarrhoea 56 6 41 2Infection 43 17 34 16Stomatitis 23 lt1 14 0Pneumonitis 2 2 1 lt1Fatigue 89 15 86 15
PA3 studyPA3 study Adverse eventsAdverse events
Moore et al JCO 2007
ADVANCED DISEASE
AccetableAccetable standard standard systemicsystemic treatmenttreatment options 2009options 2009
bullbull GEM GEM alonealonebullbull GEMGEM--erlotiniberlotinib
ndashndash registredregistred for for metastaticmetastatic PC PC onlyonly mOSmOS + 12 + 12 daysdays somesome additionaladditional toxicitytoxicity
bullbull GEMGEM--CAP CAP mOSmOS + 1 + 1 monthmonth onlyonly significantsignificant in in metameta--analysisanalysis
bullbull GEMGEM--platinumplatinum ndashndash doubtfuldoubtful effecteffect -- nownow not not significantsignificant in in metameta--
analysisanalysis significantsignificant toxicitytoxicity
ADVANCED DISEASE
SUPPORTIVE CARESUPPORTIVE CARE
Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer
SUPPORTIVE CARE
GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)
enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009
Baggrund
VTE forekommer hos ca 10 af patienter med PC
Formaringl
Undersoslashge effekt af LMWH (Klexane) i kombination med
kemoterapi mht frekvens af VTE og mOS
Inklusion
Avanceret PC ikke tidligere kemoterapi
Karnofsky
PS gt 60
Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor
2 aringr
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al ASCO 2009
Antal af VTE 15152 i observation ndash 2160 i LMWH
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al
Konklusion
LMWH er effektiv og sikker behandling til forebyggelse af
VTE hos patienter med pancreascancer
Endelige resultater paring
mOS og mTTP
afventes
SUPPORTIVE CARE
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
PA3 studyPA3 study Hazard ratios for survivalHazard ratios for survival
HR 95 CI n
Tarcevaplacebo
Performance status 0-1Performance status 2
Locally advancedDistant metastasis
Pain 20 Pain gt20
MaleFemale
Age lt65Age 65
United StatesCanada
Rest of World
HER1EGFR positiveHER1EGFR negative
HER1EGFR unknown
1
082 07-10 569
087 07-11 463056 04-08 106
094 06-14 138078 06-09 431
070 05-09 258098 08-13 296
074 06-09 298096 07-13 271
074 06-10 301093 07-12 268
071 05-09 211079 05-12 117096 07-13 241
073 04-12 74077 05-13 71086 07-11 424
Fact
ors
Moore et al JCO 2007
ADVANCED DISEASE
Events
Tarceva () n=282
Placebo () n=280
Any Grade 34 Any Grade 34Rash 72 6 29 1Diarrhoea 56 6 41 2Infection 43 17 34 16Stomatitis 23 lt1 14 0Pneumonitis 2 2 1 lt1Fatigue 89 15 86 15
PA3 studyPA3 study Adverse eventsAdverse events
Moore et al JCO 2007
ADVANCED DISEASE
AccetableAccetable standard standard systemicsystemic treatmenttreatment options 2009options 2009
bullbull GEM GEM alonealonebullbull GEMGEM--erlotiniberlotinib
ndashndash registredregistred for for metastaticmetastatic PC PC onlyonly mOSmOS + 12 + 12 daysdays somesome additionaladditional toxicitytoxicity
bullbull GEMGEM--CAP CAP mOSmOS + 1 + 1 monthmonth onlyonly significantsignificant in in metameta--analysisanalysis
bullbull GEMGEM--platinumplatinum ndashndash doubtfuldoubtful effecteffect -- nownow not not significantsignificant in in metameta--
analysisanalysis significantsignificant toxicitytoxicity
ADVANCED DISEASE
SUPPORTIVE CARESUPPORTIVE CARE
Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer
SUPPORTIVE CARE
GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)
enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009
Baggrund
VTE forekommer hos ca 10 af patienter med PC
Formaringl
Undersoslashge effekt af LMWH (Klexane) i kombination med
kemoterapi mht frekvens af VTE og mOS
Inklusion
Avanceret PC ikke tidligere kemoterapi
Karnofsky
PS gt 60
Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor
2 aringr
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al ASCO 2009
Antal af VTE 15152 i observation ndash 2160 i LMWH
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al
Konklusion
LMWH er effektiv og sikker behandling til forebyggelse af
VTE hos patienter med pancreascancer
Endelige resultater paring
mOS og mTTP
afventes
SUPPORTIVE CARE
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
Events
Tarceva () n=282
Placebo () n=280
Any Grade 34 Any Grade 34Rash 72 6 29 1Diarrhoea 56 6 41 2Infection 43 17 34 16Stomatitis 23 lt1 14 0Pneumonitis 2 2 1 lt1Fatigue 89 15 86 15
PA3 studyPA3 study Adverse eventsAdverse events
Moore et al JCO 2007
ADVANCED DISEASE
AccetableAccetable standard standard systemicsystemic treatmenttreatment options 2009options 2009
bullbull GEM GEM alonealonebullbull GEMGEM--erlotiniberlotinib
ndashndash registredregistred for for metastaticmetastatic PC PC onlyonly mOSmOS + 12 + 12 daysdays somesome additionaladditional toxicitytoxicity
bullbull GEMGEM--CAP CAP mOSmOS + 1 + 1 monthmonth onlyonly significantsignificant in in metameta--analysisanalysis
bullbull GEMGEM--platinumplatinum ndashndash doubtfuldoubtful effecteffect -- nownow not not significantsignificant in in metameta--
analysisanalysis significantsignificant toxicitytoxicity
ADVANCED DISEASE
SUPPORTIVE CARESUPPORTIVE CARE
Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer
SUPPORTIVE CARE
GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)
enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009
Baggrund
VTE forekommer hos ca 10 af patienter med PC
Formaringl
Undersoslashge effekt af LMWH (Klexane) i kombination med
kemoterapi mht frekvens af VTE og mOS
Inklusion
Avanceret PC ikke tidligere kemoterapi
Karnofsky
PS gt 60
Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor
2 aringr
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al ASCO 2009
Antal af VTE 15152 i observation ndash 2160 i LMWH
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al
Konklusion
LMWH er effektiv og sikker behandling til forebyggelse af
VTE hos patienter med pancreascancer
Endelige resultater paring
mOS og mTTP
afventes
SUPPORTIVE CARE
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
AccetableAccetable standard standard systemicsystemic treatmenttreatment options 2009options 2009
bullbull GEM GEM alonealonebullbull GEMGEM--erlotiniberlotinib
ndashndash registredregistred for for metastaticmetastatic PC PC onlyonly mOSmOS + 12 + 12 daysdays somesome additionaladditional toxicitytoxicity
bullbull GEMGEM--CAP CAP mOSmOS + 1 + 1 monthmonth onlyonly significantsignificant in in metameta--analysisanalysis
bullbull GEMGEM--platinumplatinum ndashndash doubtfuldoubtful effecteffect -- nownow not not significantsignificant in in metameta--
analysisanalysis significantsignificant toxicitytoxicity
ADVANCED DISEASE
SUPPORTIVE CARESUPPORTIVE CARE
Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer
SUPPORTIVE CARE
GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)
enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009
Baggrund
VTE forekommer hos ca 10 af patienter med PC
Formaringl
Undersoslashge effekt af LMWH (Klexane) i kombination med
kemoterapi mht frekvens af VTE og mOS
Inklusion
Avanceret PC ikke tidligere kemoterapi
Karnofsky
PS gt 60
Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor
2 aringr
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al ASCO 2009
Antal af VTE 15152 i observation ndash 2160 i LMWH
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al
Konklusion
LMWH er effektiv og sikker behandling til forebyggelse af
VTE hos patienter med pancreascancer
Endelige resultater paring
mOS og mTTP
afventes
SUPPORTIVE CARE
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
SUPPORTIVE CARESUPPORTIVE CARE
Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer
SUPPORTIVE CARE
GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)
enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009
Baggrund
VTE forekommer hos ca 10 af patienter med PC
Formaringl
Undersoslashge effekt af LMWH (Klexane) i kombination med
kemoterapi mht frekvens af VTE og mOS
Inklusion
Avanceret PC ikke tidligere kemoterapi
Karnofsky
PS gt 60
Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor
2 aringr
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al ASCO 2009
Antal af VTE 15152 i observation ndash 2160 i LMWH
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al
Konklusion
LMWH er effektiv og sikker behandling til forebyggelse af
VTE hos patienter med pancreascancer
Endelige resultater paring
mOS og mTTP
afventes
SUPPORTIVE CARE
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
Forebyggelse af venForebyggelse af venoslashoslashse se tromboembolisketromboemboliske events (VTE) ved events (VTE) ved pancreascancerpancreascancer
SUPPORTIVE CARE
GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)
enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009
Baggrund
VTE forekommer hos ca 10 af patienter med PC
Formaringl
Undersoslashge effekt af LMWH (Klexane) i kombination med
kemoterapi mht frekvens af VTE og mOS
Inklusion
Avanceret PC ikke tidligere kemoterapi
Karnofsky
PS gt 60
Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor
2 aringr
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al ASCO 2009
Antal af VTE 15152 i observation ndash 2160 i LMWH
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al
Konklusion
LMWH er effektiv og sikker behandling til forebyggelse af
VTE hos patienter med pancreascancer
Endelige resultater paring
mOS og mTTP
afventes
SUPPORTIVE CARE
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
GONKO 004 GONKO 004 trialtrialA prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH)
enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et al ASCO 2009
Baggrund
VTE forekommer hos ca 10 af patienter med PC
Formaringl
Undersoslashge effekt af LMWH (Klexane) i kombination med
kemoterapi mht frekvens af VTE og mOS
Inklusion
Avanceret PC ikke tidligere kemoterapi
Karnofsky
PS gt 60
Ingen stoslashrre bloslashdning indenfor 2 uger ingen VTE indenfor
2 aringr
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al ASCO 2009
Antal af VTE 15152 i observation ndash 2160 i LMWH
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al
Konklusion
LMWH er effektiv og sikker behandling til forebyggelse af
VTE hos patienter med pancreascancer
Endelige resultater paring
mOS og mTTP
afventes
SUPPORTIVE CARE
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al ASCO 2009
Antal af VTE 15152 i observation ndash 2160 i LMWH
SUPPORTIVE CARE
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al
Konklusion
LMWH er effektiv og sikker behandling til forebyggelse af
VTE hos patienter med pancreascancer
Endelige resultater paring
mOS og mTTP
afventes
SUPPORTIVE CARE
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
A prospective randomized trial of chemotherapy with or without the low molecular weight heparin (LMWH) enoxaparin in patients (pts) with advanced pancreatic cancer (APC) Results of the CONKO 004 trial HReiss et
al
Konklusion
LMWH er effektiv og sikker behandling til forebyggelse af
VTE hos patienter med pancreascancer
Endelige resultater paring
mOS og mTTP
afventes
SUPPORTIVE CARE
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
TreatmentTreatment of of malignantmalignant ascitesascites
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull CatumaxomabCatumaxomab TrifunctionalTrifunctional antibody 4 antibody 4 infusions infusions ipip over 6 h in ascending doses over 6 h in ascending doses
bullbull Multicenter randomized openMulticenter randomized open--label phase label phase IIIII studyIIIII study
bullbull 258 pts with symptomatic malignant 258 pts with symptomatic malignant ascitesascites due to epithelial cancerdue to epithelial cancer
SUPPORTIVE CARE
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
HeissHeiss M et al M et al CatumaxomabCatumaxomab ndashndash a new treatment option for patients a new treatment option for patients with malignant with malignant ascitesascites Ann Oncol20Suppl 7 2009 Ann Oncol20Suppl 7 2009
bullbull Subgroup analysis of 129 Subgroup analysis of 129 ovarian and 129 nonovarian and 129 non-- ovarian (gastric pancreatic ovarian (gastric pancreatic CRC etc) cancer patients CRC etc) cancer patients randomizedrandomized
bullbull AEsAEs Cytokine release Cytokine release related symptoms in 80 related symptoms in 80 mostly shortmostly short--lasting and of lasting and of grade 1grade 1--22
SUPPORTIVE CARE
0
10
20
30
40
50
60
Non-ovariancancer
Ovariancancer
CatumaxomabPlacebo
Median puncture-free survival (days)
2p lt 00001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
Pancreatic islet cell Pancreatic islet cell tumourstumours
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull SunitinibSunitinib Oral Oral multitargetedmultitargeted tyrosine tyrosine kinasekinase inhibitor used for inhibitor used for mRCCmRCC and GISTand GIST
bullbull Phase IIPhase II--study of study of sunitinibsunitinib in NETin NET11 ORR ORR of 167 in 66 pts with of 167 in 66 pts with pNETpNET
1) Kulke MH et al JCO 263403-10 2008
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Local locally advanced or metastatic Local locally advanced or metastatic wellwell--differentiated differentiated pNETpNET not amenable to not amenable to curative therapy and with disease curative therapy and with disease progression in the prior 12 monthsprogression in the prior 12 months
bullbull Primary end point PFSPrimary end point PFSbullbull SunitinibSunitinib 375 mgday or placebo375 mgday or placebo
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull 154 pts randomized154 pts randomizedbullbull Toxicity events Toxicity events sunitinibsunitinib
ndashndash Diarrhea nausea vomiting asthenia fatigueDiarrhea nausea vomiting asthenia fatiguendashndash Grade 3Grade 3--4 4 neutropenianeutropenia (12) hypertension (12) hypertension
(9) diarrhea (7) hypoglycemia (7) (9) diarrhea (7) hypoglycemia (7) palmarpalmar--plantar plantar erythrodysesthesiaerythrodysesthesia (7)(7)
Pancreatic NET
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001
Raymond E et al Phase III randomized doubleRaymond E et al Phase III randomized double--blind trial of blind trial of sunitinibsunitinib versus placebo in versus placebo in patients with progressive wellpatients with progressive well--differentiated pancreatic islet cell differentiated pancreatic islet cell tumourstumours Ann Ann Oncol20Suppl 7 2009Oncol20Suppl 7 2009
bullbull Interim analysis with Interim analysis with 73 events73 eventsndashndash 5 deaths in 5 deaths in sunitinibsunitinib
arm arm vsvs 15 in placebo 15 in placebo armarm
bullbull Study halted early Study halted early and patients on and patients on placebo given the placebo given the opportunity to cross opportunity to cross over to over to sunitinibsunitinib
Pancreatic NET
0
2
4
6
8
10
12
Medianprogressionfree survival
(months)
PlaceboSunitinib
HR 0397 2p lt0001