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Paris- RPReims
RennesTours
MarseilleMontpellier
Lyon
Nice
Lille
Strasbourg
Bordeaux
DijonBesançon
Nantes
Toulouse
Poitiers
Angers
Nancy
Caen
Rouen
Clermont-Ferrand
GSF: Groupe Sarcome FrançaisGSF: Groupe Sarcome FrançaisGETO: Groupe d’Etudes des Tumeurs OsseusesGETO: Groupe d’Etudes des Tumeurs Osseuses
VillejuifN = 36 institutionsN = 36 institutions
Sarcoma Database:Sarcoma Database:3300 pts3300 pts
Frozen tissue bank:Frozen tissue bank:1300 sarcomas1300 sarcomas
Sarcome 01 Sarcome 01 Euro-Ewing 99Euro-Ewing 99PI :PI : Dr O. Oberlin – VillejuifDr O. Oberlin – Villejuif
EORTCEORTC SFCESFCE GPOHGPOH UKCCSGUKCCSG TotalTotal
NN 567567 18741874
Molecular analysis on Iry: 448 patients (79 %)BM: 326 patients (57%)
30 sept 0630 sept 06
Suspension of R1 randomizationSuspension of R1 randomization0
100
200
300
400
500
600
1 11 21 31 41 51 61 71 81
Patients prévus
Patients inclus
567
525
Sarcome 02 Sarcome 02 PALSAR IIPALSAR II
PI :PI : Dr N B BUI – BordeauxDr N B BUI – Bordeaux
Arm 1 2 MAID
RA
ND
OM
ISA
TIO
N
4 MAID
SD / RP/ RC +/- surgery
PD
Arm 2 1 MAID – MICE + PBSC
Main end-point: Main end-point: overall survivaloverall survivalStatistical hypothesis: Statistical hypothesis: 3-yr OS: 40% vs 15% (N® per arm: 50)3-yr OS: 40% vs 15% (N® per arm: 50)
October 06: October 06: N = 207 patientsN = 207 patients N® = 65/100 patientsN® = 65/100 patients
Sarcome 03 Sarcome 03 OsteosarcomaOsteosarcoma
PI :PI : A Le Cesne – VillejuifA Le Cesne – Villejuif
Localized operableosteosarcoma
API-AI regimen4 CT courses
Main end-point: Main end-point: histological response ratehistological response rate
Good histological response: Good histological response: 37%37% ASCO 06ASCO 062-yr overall survival:2-yr overall survival: 86% 86% 2-yr PFS2-yr PFS 74%74%
Follow-upFollow-up
Inclusion Curve
40
47
0
5
10
15
20
25
30
35
40
45
50
Nu
mb
er o
f p
atie
nts
Theoric
Real
Sarcome 04 Sarcome 04 EWINGEWING
PI :PI : O Oberlin – VillejuifO Oberlin – Villejuif
D1 D8 D15D1 D8 D15 D21 D21 D28/1 D8 D15 D21 D28 D28/1 D8 D15 D21 D28
CDDPCDDP
VP-16VP-16
Main end-point: Main end-point: Objective response rateObjective response rateStatistical hypothesis: Statistical hypothesis: Simon: at least 6/29 OR Simon: at least 6/29 OR
October 2006 = 44/45October 2006 = 44/45ASCO 07ASCO 07
Sarcome 05 Sarcome 05 DesminibDesminib
PI :PI : JY Blay – LyonJY Blay – Lyon
Progressive AF/Desmoid TGlivec®: 400 mg/d800 mg/d if PDDuration: one year
Main end-point: Main end-point: 3-month PFS (at least 7 patients not PD)3-month PFS (at least 7 patients not PD)At 3 month: At 3 month: 1 CR, 1 PR, 31 SD, 5 PD 1 CR, 1 PR, 31 SD, 5 PD ASCO 06ASCO 066-m PFS 73%; 1-yr PFS 69%6-m PFS 73%; 1-yr PFS 69%Translational research ongoingTranslational research ongoing
imatinibimatinibRandomRandom
NSAIDNSAID
courbes des inclusions
0
5
10
15
20
25
30
35
40
45
août-
04
oct-
04
déc-0
4
févr-
05
avr-
05
juin
-05
août-
05
oct-
05
déc-0
5
févr-
06
avr-
06
juin
-06
août-
06
oct-
06
déc-0
6
févr-
07
avr-
07
juin
-07
août-
07
No
mb
re d
e p
ati
en
ts
Théorique
Réelle
40 39
Sarcome 06: Sarcome 06: AngiotaxAngiotax
PI :PI : N Penel – LilleN Penel – Lille
AngiosarcomaAngiosarcoma2nd/3rd CT line2nd/3rd CT line
Weekly taxol: 80 mg/wWeekly taxol: 80 mg/w3 weeks on, 1 off3 weeks on, 1 off
Main end-point: Main end-point: Objective response rateObjective response rateStatistical hypothesis: Statistical hypothesis: Simon two step: 15 + 10 patientsSimon two step: 15 + 10 patients
at least 6/25 OR at least 6/25 OR Secondary end-point: Secondary end-point: PFS, OS, tolerancePFS, OS, toleranceTranslational researchTranslational research
ASCO 2007ASCO 2007
courbes des inclusions
0
5
10
15
20
25
30
35
Théorique
Réelle
30 30
Sarcome 07 Sarcome 07 TaxogemTaxogem
PI :PI : F. Duffaud – MarseilleF. Duffaud – MarseilleP. Pautier - VillejuifP. Pautier - Villejuif
® phase II® phase IILeiomyosarcomaLeiomyosarcoma
Uterine vs otherUterine vs other2nd CT line2nd CT line
N = 40 + 40N = 40 + 40
Main end-point: Main end-point: ORORSecondary end-point: Secondary end-point: PFS, OS, tolerance, QOLPFS, OS, tolerance, QOL
N = 13/80N = 13/80
Gemzar. n°1
Gemzar n°2
Gemzar n°3
Randomisation
Gemzar
J1 J8 J15
J22 J1=J29
J1 J8
BRAS A
BRAS B
Granocyte J9-J15
J15
CYCLE N CYCLE N+1
Gemzar + TXT
J1=J22
PI (FSG) :PI (FSG) : A Le Cesne – VillejuifA Le Cesne – Villejuif
Sarcome 08:Sarcome 08:Adjuvant GISTAdjuvant GISTEORTC 62024EORTC 62024
October 2006October 2006N = 418 N = 418
No adjuvantG livec
G livec400m g/j 2 years
R andom ization
G IST CD117+Definitive surgery
Participating French centers : 42Participating French centers : 42Mutational analysis: 70%Mutational analysis: 70%
Courbe des inclusions
0
20
40
60
80
100
120
140
Mois
No
mb
re d
e p
atie
nts
Théorique
Réelle
100127
0
2
4
6
8
10
12
14
16
18
20
Inclusions centres traités/non traités
non traité
traité
PI :PI : F Duffaud – Curie / L Brugieres - VillejuifF Duffaud – Curie / L Brugieres - Villejuif
Intergroup SFCE/GSF/GETOIntergroup SFCE/GSF/GETO Adult/children OS – phase III ZoledronateAdult/children OS – phase III Zoledronate
N = 470N = 4703-yr EFS > 13%3-yr EFS > 13%in exp armin exp arm
TranslationalTranslationalresearchresearch
Sarcome 09 Sarcome 09 OS 2006OS 2006
M T X - VP- I FO A PI - A I M T X - VP- I FO
Z ometa
M T X ou A PI
au choix
du centreA PI - A I
Z ometa
BR M R BR M R BR M R BR M R
M T XVP-IFO A PI VP-IFO
VP- I FO
Z ometa
M T X
VP- I FO
Z ometa
M T X
CP- A d
M T X
CP- A d
Z ometa
A PI
Z ometa
M T X ou A PI
au choix
du centre
<18 ans 18- 25 ans >25 ans
S ans Z ometa
<18 ans 18- 25 ans >25 ans
A vec Z ometa
Randomisat ion
PI:PI: P Pautier – VillejuifP Pautier – Villejuif
Uterine leiomyoS, carcinoS, high grade endometrial SUterine leiomyoS, carcinoS, high grade endometrial S
N = 52 / 256N = 52 / 2563-yr EFS > 20% in experimental arm3-yr EFS > 20% in experimental arm
Sarc-Gyn 1 Sarc-Gyn 1 Adjuvant CTAdjuvant CT
Arm AArm A
4 x API4 x API RTE 45 Gy RTE 45 Gy ++ Brachytherapy 15 Gy Brachytherapy 15 Gy
A (50), I ( 6), C (75)A (50), I ( 6), C (75)
Surgery < 6 wSurgery < 6 w RR
RTE 45 Gy RTE 45 Gy ++ Brachytherapy 15 Gy Brachytherapy 15 Gy- Arm BArm B
BFR 14 trial - BFR 14 trial - Advanced GISTAdvanced GIST (June 2002)(June 2002)
StopStop
Imatinib Imatinib Non PD RNon PD R
ImatinibImatinib
PI :PI : J.Y Blay – LyonJ.Y Blay – LyonA. Le Cesne - VillejuifA. Le Cesne - Villejuif
N patients included in October 2005:N patients included in October 2005: 271271
1) 1) N randomized (interrupted) pts at 1 year: 58 (ASCO 04,05)N randomized (interrupted) pts at 1 year: 58 (ASCO 04,05)
Stop imatinib arm:Stop imatinib arm: 3232imatinib arm:imatinib arm: 2626
2) 2) N randomized (ongoing) pts at 3 years:N randomized (ongoing) pts at 3 years: 32 (ASCO 07) 32 (ASCO 07)
BFR14 : Survie sans progression des randomisés à 1 an
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
0 6 12 18 24 30 36 42
Délai depuis randomisation à 1 an (mois)
Pro
ba
bil
ité
de
su
rv
ie
Log-rank test : p < 0.0001
CONT group10 evts / 26 patientsMédiane SSP: 28.3 moisSTOP group
28 evts / 32 patientsMédiane SSP : 6.1 mois
AB1010 first line - AB1010 first line - Advanced GISTAdvanced GIST
Day 1Day 1Preclinical efficacy Preclinical efficacy
profile profile > to IM> to IM
IC50 < 0.005 µMIC50 < 0.005 µMvsvs
IC50 = 0.02 µMIC50 = 0.02 µM
Phase IIPhase IIAB1010: 7.5 mg/kgAB1010: 7.5 mg/kg
4 centers4 centers
N = 25N = 25(06/05 to 11/06)(06/05 to 11/06)
ASCO 2007ASCO 2007
M6M6
Day 1Day 1
M1M1
PI :PI : A. Le Cesne - VillejuifA. Le Cesne - Villejuif