Humblet ASCO 2007 – Draft CONFIDENTIAL Association of skin toxicity (ST) severity with clinical outcomes and health-related quality of life (HRQoL) with

Humblet ASCO 2007 – Draft CONFIDENTIAL

Association of skin toxicity (ST) severity Association of skin toxicity (ST) severity with clinical outcomes and health-related with clinical outcomes and health-related quality of life (HRQoL) with panitumumab quality of life (HRQoL) with panitumumab

(Pmab)(Pmab)

Yves Humblet,Yves Humblet,11 Marc Peeters, Marc Peeters,22 Salvatore Artale, Salvatore Artale,33 Alain Hendlisz, Alain Hendlisz,44 Bart Neyns, Bart Neyns,55 A. Sobrero, A. Sobrero,66 Michael Wolf, Michael Wolf,77 Michael Woolley, Michael Woolley,77 Rafael Amado,Rafael Amado,7 7 Eric Van CutsemEric Van Cutsem88

Abstract #4038Abstract #4038

11St-Luc University Hospital, Brussels, Belgium; St-Luc University Hospital, Brussels, Belgium; 22Ghent University Hospital, Ghent, Belgium; Ghent University Hospital, Ghent, Belgium; 33Ospedale Niguarda Ca’ Granda, Milan, Italy; Ospedale Niguarda Ca’ Granda, Milan, Italy; 44Jules Bordet Institute, Brussels, Jules Bordet Institute, Brussels, Belgium; Belgium; 55AZ Vrije Universiteit Brussel, Brussels, Belgium; AZ Vrije Universiteit Brussel, Brussels, Belgium; 66Ospedale San Martino, Genoa, Italy; Ospedale San Martino, Genoa, Italy; 77Amgen Inc., Thousand Oaks, CA; Amgen Inc., Thousand Oaks, CA; 88University Hospital Gasthuisberg, University Hospital Gasthuisberg,

Leuven, BelgiumLeuven, Belgium


IntroductionIntroduction

• Skin toxicity severity has been shown to be associated with efficacy in patients with metastatic colorectal cancer (mCRC) receiving anti- epidermal growth factor receptor (EGFr) therapySkin toxicity severity has been shown to be associated with efficacy in patients with metastatic colorectal cancer (mCRC) receiving anti- epidermal growth factor receptor (EGFr) therapy

• Panitumumab is a fully human monoclonal antibody directed against the EGFr and is indicated for use in patients with mCRC who progressed on or following standard chemotherapyPanitumumab is a fully human monoclonal antibody directed against the EGFr and is indicated for use in patients with mCRC who progressed on or following standard chemotherapy 1,21,2

• This phase 3, randomized controlled trial demonstrated that panitumumab plus best supportive care (BSC) improved progression-free survival (PFS) compared with BSC alone in This phase 3, randomized controlled trial demonstrated that panitumumab plus best supportive care (BSC) improved progression-free survival (PFS) compared with BSC alone in chemorefractory mCRC patientschemorefractory mCRC patients33

• We conducted an exploratory analysis to evaluate the We conducted an exploratory analysis to evaluate the association of skin toxicity severity with PFS, overall survival (OS), disease-related symptoms and HRQOL with panitumumab association of skin toxicity severity with PFS, overall survival (OS), disease-related symptoms and HRQOL with panitumumab treatmenttreatment


RRAANNDDOOMMIIZZEE

Study DesignStudy Design

1:11:1

Panitumumab PD* Follow-up6.0 mg/kg Q2W+ BSC

BSC PD* Follow-upOptional Optional

Panitumumab Panitumumab Crossover StudyCrossover Study

Stratification:Stratification:

• ECOG score: 0-1 vs. 2ECOG score: 0-1 vs. 2

• Geographic region (Western Europe vs. Central Geographic region (Western Europe vs. Central and Eastern Europe vs. the rest of world)and Eastern Europe vs. the rest of world)

Primary Primary EndpointEndpoint

• Progression-free survival (per blinded central radiology Progression-free survival (per blinded central radiology assessment of modified RECIST criteria)assessment of modified RECIST criteria)

Secondary Secondary EndpointsEndpoints

• Overall survival time and best overall objective response Overall survival time and best overall objective response (central radiology; testing prespecified)(central radiology; testing prespecified)

• Safety, disease-related symptoms, and HRQoLSafety, disease-related symptoms, and HRQoL

*PD= progressive disease


• Metastatic colorectal adenocarcinoma (mCRC)Metastatic colorectal adenocarcinoma (mCRC)

• ECOG score 0 to 2ECOG score 0 to 2

• Radiologic documentation of disease progression after Radiologic documentation of disease progression after fluoropyrimidine, irinotecan, and oxaliplatinfluoropyrimidine, irinotecan, and oxaliplatin

– During or within 6 months following most recent chemotherapy During or within 6 months following most recent chemotherapy regimenregimen

– 2 or 3 prior regimens2 or 3 prior regimens

• EGFr membrane staining on EGFr membrane staining on ≥≥ 1% tumor cells (IHC, central laboratory) 1% tumor cells (IHC, central laboratory)

• Adequate hematologic, renal, and hepatic functionAdequate hematologic, renal, and hepatic function

• No symptomatic brain metastasesNo symptomatic brain metastases

• No chemotherapy within 30 days before randomizationNo chemotherapy within 30 days before randomization

• No prior anti-EGFR agent therapyNo prior anti-EGFR agent therapy

Key Eligibility CriteriaKey Eligibility Criteria


AssessmentsAssessments

• Skin toxicity was measured by:Skin toxicity was measured by:

– CTCAE grading criteria version 3.0 (modified for dermatology toxicities) CTCAE grading criteria version 3.0 (modified for dermatology toxicities) andand

– Modified Dermatology Life Quality Index (mDLQI) (Modified Dermatology Life Quality Index (mDLQI) (See Table 1)See Table 1)

• CRC symptoms were measured by the NCCN/FACT CRC symptom index CRC symptoms were measured by the NCCN/FACT CRC symptom index (FCSI) ((FCSI) (See Table 1)See Table 1)

• HRQoL was measured by the EQ-5D and EORTC QLQ-C30 Global QoL HRQoL was measured by the EQ-5D and EORTC QLQ-C30 Global QoL subscale (subscale (See Table 1)See Table 1)


Table 1. Patient Reported OutcomesTable 1. Patient Reported Outcomes

PRO InstrumentPRO Instrument MeasurementMeasurement DescriptionDescription Assessment Assessment ScheduleSchedule

Modified Modified Dermatology Life Dermatology Life Quality Index Quality Index (mDLQI)(mDLQI)

Problems due Problems due to skin to skin conditioncondition

3 items measuring problems and bother with skin 3 items measuring problems and bother with skin condition. Scores range from 0 to 100 with higher condition. Scores range from 0 to 100 with higher scores indicating less problems/botherscores indicating less problems/bother

Baseline, Q2W Baseline, Q2W during treatment, during treatment, and at the 30-day and at the 30-day safety follow-up safety follow-up visit visit after the last after the last protocol directed protocol directed therapy therapy

NCCN/FACT NCCN/FACT Colorectal Colorectal Symptom Index Symptom Index (FCSI)(FCSI)

CRC CRC SymptomsSymptoms

A brief symptom index comprising of the most A brief symptom index comprising of the most clinically relevant (clinician rated) symptoms for clinically relevant (clinician rated) symptoms for assessing symptomatic response to treatment for assessing symptomatic response to treatment for CRC. Scores range from 0 to 100 with higher scores CRC. Scores range from 0 to 100 with higher scores indicating less symtomatologyindicating less symtomatology

EUROQOL (EQ5D) EUROQOL (EQ5D) Health IndexHealth Index

HRQOLHRQOL Provides a preference-weighted assessment of Provides a preference-weighted assessment of overall QOL across five dimensions: mobility, self–overall QOL across five dimensions: mobility, self–care, usual activity, pain or discomfort, and anxiety care, usual activity, pain or discomfort, and anxiety or depression. Scores range from 0 to 1 (0 = death, or depression. Scores range from 0 to 1 (0 = death, 1 = perfect health)1 = perfect health)

Baseline, monthly Baseline, monthly during treatment, during treatment, and at the 30-day and at the 30-day safety follow-up safety follow-up visit visit after the last after the last protocol directed protocol directed therapy therapy

EUROQOL (EQ5D) EUROQOL (EQ5D) Visual Analog Visual Analog Scale (VAS)Scale (VAS)

HRQOLHRQOL Measures overall health status. Scores range from Measures overall health status. Scores range from 0 to 100 with 0 representing worst imaginable 0 to 100 with 0 representing worst imaginable health state and 100 representing best imaginable health state and 100 representing best imaginable health state health state

EORTC QLQ-C30 EORTC QLQ-C30 Global Health Global Health Status/QOL ScaleStatus/QOL Scale

HRQOLHRQOL 2 items of the EORTC QLQ-C30 measuring overall 2 items of the EORTC QLQ-C30 measuring overall health status and overall QOL. Scores range from 0 health status and overall QOL. Scores range from 0 to 100 with higher scores indicating better HRQOLto 100 with higher scores indicating better HRQOL


Overall Treatment EffectOverall Treatment Effect

• PRO Analysis set included all patients who had at least 1 post-baseline PRO assessmentPRO Analysis set included all patients who had at least 1 post-baseline PRO assessment

Association of skin toxicity with efficacy and PROsAssociation of skin toxicity with efficacy and PROs

• Analyses of skin toxicity by CTCAE grading criteria and mDLQI were restricted to patients in Analyses of skin toxicity by CTCAE grading criteria and mDLQI were restricted to patients in the panitumumab arm who were progression-free for at least 28 days to allow for onset of skin the panitumumab arm who were progression-free for at least 28 days to allow for onset of skin toxicity and toxicity and

– had had grade 1 skin toxicity (for CTCAE) or grade 1 skin toxicity (for CTCAE) or

– had at least 1 post-baseline PRO assessment (mDLQI)had at least 1 post-baseline PRO assessment (mDLQI)

• Dichotomization of PFS for degree of being bothered was explored using all possible cut Dichotomization of PFS for degree of being bothered was explored using all possible cut points of mDLQI (based on Cox model)points of mDLQI (based on Cox model)

• Hazard ratios (HR) adjusted for randomization factors and correlation analyses were used to Hazard ratios (HR) adjusted for randomization factors and correlation analyses were used to determine relationships between PFS and OS to skin toxicity, and skin toxicity to colorectal determine relationships between PFS and OS to skin toxicity, and skin toxicity to colorectal cancer symptoms and overall HRQoLcancer symptoms and overall HRQoL

Statistical AnalysesStatistical Analyses


Association of skin toxicity with efficacy and PROs (Association of skin toxicity with efficacy and PROs (cont.cont.))

• Missing PRO data were imputed using 2 imputation methods:Missing PRO data were imputed using 2 imputation methods:

– The last value carried forward (LVCF) method, in which missing The last value carried forward (LVCF) method, in which missing observations were replaced with the LVCF, or zero value carried observations were replaced with the LVCF, or zero value carried forward at death; andforward at death; and

– The slope method, in which a forward linear interpolation of observed The slope method, in which a forward linear interpolation of observed data was utilized to impute missing datadata was utilized to impute missing data

Statistical Analyses (Statistical Analyses (cont.cont.))


ResultsResultsDisposition and Patient Analysis SetsDisposition and Patient Analysis Sets

PanitumumabPanitumumabPlus BSCPlus BSC

BSC BSC AloneAlone

Total Randomized, nTotal Randomized, n 231231 232232

PRO All Enrolled Analysis Set, nPRO All Enrolled Analysis Set, n 207207 184184

Patients Completing EQ-5D, nPatients Completing EQ-5D, n Week 4Week 4 189189 129129 Week 8Week 8 111111 4747 Week 12Week 12 9191 1414 Week 16Week 16 6262 77

Patients Completing FACT CRC Subscale, nPatients Completing FACT CRC Subscale, n Week 4Week 4 190190 130130 Week 8Week 8 112112 4848 Week 12Week 12 9090 1414 Week 16Week 16 6262 77

Patients Completing mDLQI Subscale, nPatients Completing mDLQI Subscale, n Week 4Week 4 189189 128128 Week 8Week 8 111111 4848 Week 12Week 12 9090 1313 Week 16Week 16 6262 66


Demographics and Disease CharacteristicsDemographics and Disease CharacteristicsPRO All Enrolled Analysis SetPRO All Enrolled Analysis Set

PanitumumabPanitumumabPlus BSCPlus BSC(N=207)(N=207)

BSC AloneBSC Alone

(N=184)(N=184)

Sex – n (%)Sex – n (%)MenMen 137 (66)137 (66) 119 (65)119 (65)

Median (min, max) age – yearsMedian (min, max) age – years 61 (27, 79)61 (27, 79) 63 (32, 83)63 (32, 83)

Age Categories – years Age Categories – years < 65 < 65 ≥≥ 65 65

124 (60)124 (60)83 (40)83 (40)

109 (59)109 (59)75 (41)75 (41)

ECOG status – n (%)ECOG status – n (%)0-10-1≥≥ 2 2aa

185 (89)185 (89)22 (11)22 (11)

160 (87)160 (87)24 (13)24 (13)

Number of metastatic sites – n (%)Number of metastatic sites – n (%)1-21-23-53-5

147 (71)147 (71)60 (29)60 (29)

126 (69)126 (69)56 (31)56 (31)

Prior adjuvant chemotherapy – n (%)Prior adjuvant chemotherapy – n (%) 75 (36)75 (36) 69 (38)69 (38)

Prior chemotherapy – n (%)Prior chemotherapy – n (%)At least 2 linesAt least 2 linesAt least 3 lines At least 3 lines 206 (100)206 (100)

77 (37)77 (37)184 (100)184 (100)

66 (36)66 (36)

aOne patient had ECOG score of 3


The mDLQI-Bother Score Indicated That Panitumumab Patients Were More Bothered By Their Skin Condition

Mean (+/- SE)

Overall Treatment EffectOverall Treatment Effect

Week

Responses range from 0 to 100 with a higher score indicating a better quality of life.

Mea

n D

LQ

I-b

oth

er s

core

23.0

33.0

43.0

53.0

63.0

73.0

83.0

93.0

103.0

Base 5 9 13 17 21 25 29 33 37 41 45 48

Panitumumab Plus BSC n=

BSC Alone n=

207

184


EQ

5D

He

alth

In

de

x D

iffe

ren

ce

-0.10-0.08-0.06-0.04-0.020.000.020.040.060.080.100.120.140.160.180.20

Week4 8 12 16

MCID

MCID

Difference (95% CI) in HRQOL Scores (EQ-5D) at Difference (95% CI) in HRQOL Scores (EQ-5D) at Prespecified Timepoints for Panitumumab minus BSC Prespecified Timepoints for Panitumumab minus BSC

Patients (Primary PRO Analysis)Patients (Primary PRO Analysis)

• LVCF imputation method used for missing PRO data• The yellow line at -0.08 represents a minimum clinical important difference (MCID) anchored to a ½ point change in ECOG score

• Although panitumumab patients were more bothered by their skin conditions, HRQOL Although panitumumab patients were more bothered by their skin conditions, HRQOL scores were numerically in favor of panitumumabscores were numerically in favor of panitumumab

Difference in EQ-5D Scores (panitumumab- BSC)Difference in EQ-5D Scores (panitumumab- BSC)Panitumumab N=207Panitumumab N=207BSC N=184BSC N=184


Difference (95% CI) in CRC Symptom Scores (FCSI) at Difference (95% CI) in CRC Symptom Scores (FCSI) at Prespecified Timepoints for Panitumumab minus BSC Prespecified Timepoints for Panitumumab minus BSC

Patients (Primary PRO Analysis)Patients (Primary PRO Analysis)

• LVCF imputation method used for missing PRO data• The yellow line at -3.94 represents a minimum clinical important difference (MCID) anchored to a ½ point change in ECOG score

• Although panitumumab patients were more bothered by their skin condition, Although panitumumab patients were more bothered by their skin condition, disease-relateddisease-related symptom scores were numerically in favor of panitumumabsymptom scores were numerically in favor of panitumumab

Week4 8 12 16

FCS

IDiff

eren

ce

-4.0-3.0-2.0-1.00.01.02.03.04.05.06.07.08.09.0

10.011.012.013.014.0

Difference in FCSI scores (panitumumab- BSC)Difference in FCSI scores (panitumumab- BSC)Panitumumab N=207Panitumumab N=207BSC N=184BSC N=184

MCID

MCID


Time to Onset of Worst Severity Skin Time to Onset of Worst Severity Skin ToxicityToxicity

• Among all patients:Among all patients:

– The median time (95% CI) to most severe skin toxicity was 15 The median time (95% CI) to most severe skin toxicity was 15 (14,16) days (Kaplan-Meier method)(14,16) days (Kaplan-Meier method)

• The worst severity of skin toxicity may occur beyond 28 days, The worst severity of skin toxicity may occur beyond 28 days, thus lead-time bias cannot be completely eliminatedthus lead-time bias cannot be completely eliminated


Events / N (%) Medianin Weeks

Grade 2-4 121 / 144 ( 84 ) 10.0Grade 1 53 / 56 ( 95 ) 8.0

Program: /stat/amg954/onc/20020408/analysis/ectd/stats/post_hoc/ASCO07/Humblet/Skin_g1_234.sasOutput: graphs/PFSc.Tx_sk_g1_234LM.cgm (Date Generated:14MAY07:13:39:35)

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0 4 8 12 16 20 24 28 32 36 40 44 48 52Patients at risk:

Grade 2-4

Grade 1

144 144 87 62 41 32 24 16 11 7 4 1 1

56 56 28 14 8 8 7 3 2 1 1 1 0

Progression-Free Survival by Worst Severity of Skin Toxicity in Progression-Free Survival by Worst Severity of Skin Toxicity in

Panitumumab Patients (Landmark Analysis)Panitumumab Patients (Landmark Analysis)

• PanitumumabPanitumumab patients with worst grade of 2-4 had better progression free survival patients with worst grade of 2-4 had better progression free survival vs those with a worst grade of 1vs those with a worst grade of 1

hazard ratio (grade 2-4:1)=0.66

p=0.01

Landmark Analysis set included patients who were progression free for ≥ 28 days

Association of Skin Toxicity with OutcomesAssociation of Skin Toxicity with Outcomes


Events / N (%) Medianin Months

Grade 2-4 113 / 144 ( 78 ) 7.9Grade 1 49 / 56 ( 88 ) 5.9

Program: /stat/amg954/onc/20020408/analysis/ectd/stats/post_hoc/ASCO07/Humblet/Skin_g1_234.sasOutput: graphs/OS.Tx_sk_g1_234LM.cgm (Date Generated:14MAY07:13:39:35)

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Months from Randomization

0 2 4 6 8 10 12 14 16 18 20 22 24Patients at risk:

Grade 2-4

Grade 1

144 134 115 93 66 44 31 19 7 3 3 2

56 49 33 24 16 10 6 4 2 1 1 0

Overall Survival by Worst Severity of Skin Toxicity Overall Survival by Worst Severity of Skin Toxicity in the Panitumumab Patients (Landmark Analysis) in the Panitumumab Patients (Landmark Analysis)

hazard ratio (grade 2-4:1)=0.68

p=0.03

• PanitumumabPanitumumab patients with worst grade of 2-4 had better overall survival vs patients with worst grade of 2-4 had better overall survival vs those with a worst grade of 1those with a worst grade of 1

Landmark Analysis set included patients who were progression free for ≥ 28 days


Events / N (%) Medianin Weeks

DLQI <= 66.667 127 / 150 ( 85 ) 11.9DLQI > 66.667 38 / 40 ( 95 ) 7.7

Program: /stat/amg954/onc/20020408/analysis/ectd/stats/post_hoc/ASCO07/Humblet/DLQI.sasOutput: graphs/PFS_DLQI_max.cgm (Date Generated:14MAY07:13:39:59)

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Weeks from Randomization

0 4 8 12 16 20 24 28 32 36 40 44 48 52Patients at risk:

DLQI <= 66.667

DLQI > 66.667

150 150 94 69 47 38 30 19 13 8 5 2 1

40 40 17 6 2 2 1 0 0 0 0 0 0

Progression-Free Survival by Minimum Post-Baseline mDLQI Progression-Free Survival by Minimum Post-Baseline mDLQI Score in the Panitumumab Patients (Landmark Analysis)Score in the Panitumumab Patients (Landmark Analysis)

• Panitumumab patients with a minimum post-baseline mDLQI score Panitumumab patients with a minimum post-baseline mDLQI score ≤ 66.667≤ 66.667 (more (more bothered by their skin toxicity)bothered by their skin toxicity) had longer progression free survivalhad longer progression free survival

hazard ratio (≤66.667:>66.667)=0.41

p<0.0001

Landmark Analysis set included patients who were progression free for ≥ 28 days; at least 1 post-baseline PROassessment was also required.mDLQI nadir timing: mean – 30 days, median – 14 days, 75th Percentile – 28 days


Events / N (%) Medianin Months

DLQI <= 66.667 119 / 150 ( 79 ) 8.2DLQI > 66.667 37 / 40 ( 93 ) 3.4

Program: /stat/amg954/onc/20020408/analysis/ectd/stats/post_hoc/ASCO07/Humblet/DLQI.sasOutput: graphs/OS_DLQI_max.cgm (Date Generated:14MAY07:13:39:59)

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0 2 4 6 8 10 12 14 16 18 20 22 24Patients at risk:

DLQI <= 66.667

DLQI > 66.667

150 144 127 102 73 49 34 22 9 4 4 2

40 30 17 11 5 3 2 0 0 0 0 0

Overall Survival by Minimum Post-Baseline mDLQI Score in Overall Survival by Minimum Post-Baseline mDLQI Score in the Panitumumab Patients (Landmark Analysis) the Panitumumab Patients (Landmark Analysis)

hazard ratio (≤66.667:>66.667)=0.35

p<0.0001

• Panitumumab patients with a minimum post-baseline mDLQI score Panitumumab patients with a minimum post-baseline mDLQI score ≤ 66.667≤ 66.667 (more (more bothered by their skin toxicity)bothered by their skin toxicity) had longer overall survivalhad longer overall survival

Landmark Analysis set included patients who were progression free for ≥ 28 days; at least 1 post-baseline PROassessment was also required.mDLQI nadir timing: mean – 30 days, median – 14 days, 75th Percentile – 28 days


Minimum Post-Baseline mDLQI Bother Score Association Minimum Post-Baseline mDLQI Bother Score Association with Median Post-Baseline Patient-Reported Outcomes with Median Post-Baseline Patient-Reported Outcomes

EQ-5D EQ-5D indexindex

EQ-5D VASEQ-5D VAS EORTC EORTC GlobalGlobal

FCSIFCSI

mDLQImDLQIBotherBother

-0.24-0.24(p=0.0006)(p=0.0006)

-0.17-0.17(p=0.01)(p=0.01)

-0.08-0.08(p=0.25)(p=0.25)

-0.13-0.13(p=0.06)(p=0.06)

EQ-5D indexEQ-5D index 0.610.61(p<.0001)(p<.0001)

0.600.60(p<.0001)(p<.0001)

0.710.71(p<.0001)(p<.0001)

EQ-5D VASEQ-5D VAS 0.790.79(p<.0001)(p<.0001)

0.700.70(p<.0001)(p<.0001)

EORTC GlobalEORTC Global 0.740.74(p<.0001)(p<.0001)

PRO All Enrolled Analysis set, panitumumab patients only.Pearson correlation coefficients are shown with p-values in parentheses.NOTES: Bother = the mDLQI “bother” item; EQ-5D Index = EQ-5D Index; EQ-5D VAS = EQ-5D Visual Analog Store; EORTC Global = EORTC QLQ-C30 Global Quality of Life Scale; FCSI = FACT/NCCN Colorectal Cancer Symptom Index

• In the panitumumab patients, lower mDLQI scores (more skin bother) were In the panitumumab patients, lower mDLQI scores (more skin bother) were associated with higher HRQOL scores (improved HRQoL)associated with higher HRQOL scores (improved HRQoL)


ConclusionsConclusions

• As expected, panitumumab patients reported being more bothered by their skin As expected, panitumumab patients reported being more bothered by their skin conditions than BSC patients; however, CRC symptoms and HRQOL scores conditions than BSC patients; however, CRC symptoms and HRQOL scores trended in favor of panitumumab vs BSCtrended in favor of panitumumab vs BSC

– Based on the minimal clinical important difference, a negative effect with Based on the minimal clinical important difference, a negative effect with panitumumab treatment could be excludedpanitumumab treatment could be excluded

• From this exploratory analysis of data from a phase 3 trial, improved PFS, From this exploratory analysis of data from a phase 3 trial, improved PFS, overall survival, CRC symptomalogy, and HRQOL were associated with worse overall survival, CRC symptomalogy, and HRQOL were associated with worse skin toxicity as measured by the CTCAE grading scale and mDLQI.skin toxicity as measured by the CTCAE grading scale and mDLQI.

• These findings support the role of skin toxicity severity as a pharmacodynamic These findings support the role of skin toxicity severity as a pharmacodynamic marker of on-target activity that appears to be associated with clinical benefit. marker of on-target activity that appears to be associated with clinical benefit. Further analyses are being conducted to explore the predictive value of early Further analyses are being conducted to explore the predictive value of early onset of skin toxicity severity (see abstract #4134, poster #P5 by Berlin et al.)onset of skin toxicity severity (see abstract #4134, poster #P5 by Berlin et al.)


ReferencesReferences

1.1. Foon KA, Yang X-D, Weiner LM, et al. Preclinical and clinical Foon KA, Yang X-D, Weiner LM, et al. Preclinical and clinical evaluations of ABX-EGF, a fully human anti-epidermal growth factor evaluations of ABX-EGF, a fully human anti-epidermal growth factor receptor antibody. Int J Radiat Oncol Biol Phys 2004:58:984-990.receptor antibody. Int J Radiat Oncol Biol Phys 2004:58:984-990.

2.2. VectibixVectibixTMTM Prescribing Information, Amgen Inc. Thousand Oaks CA; Prescribing Information, Amgen Inc. Thousand Oaks CA; 2006.2006.

3.3. Van Cutsem E, Peeters M, Siena S, et al. An open-label, randomized, Van Cutsem E, Peeters M, Siena S, et al. An open-label, randomized, phase 3 clinical trial of panitumumab plus best supportive care phase 3 clinical trial of panitumumab plus best supportive care versus best supportive care in patients with chemotherapy-versus best supportive care in patients with chemotherapy-refractoryrefractory metastatic colorectal cancer. J Clin Oncol 2007;25:1658-metastatic colorectal cancer. J Clin Oncol 2007;25:1658-1664.1664.

Documents

Humblet ASCO 2007 – Draft CONFIDENTIAL Association of skin toxicity (ST) severity with clinical outcomes and health-related quality of life (HRQoL) with