Data on panitumumab

in combination with chemotherapy

in the 1st-line treatment of mCRC

Prof Jim Cassidy

Glasgow University
Scotland
 Introduction
• Panitumumab is indicated as monotherapy for the
treatment of patients with EGFR-expressing
metastatic colorectal carcinoma with non-mutated
(wild-type) KRAS after failure of fluoropyrimidine-
oxaliplatin and irinotecan-containing chemotherapy
regimens

• Initial studies performed in chemorefractory patients

demonstrated activity and efficacy, and the agent was
approved for patients who had progressed after
standard therapy

Amgen Europe B.V. Vectibix® Summary of Product Characteristics. 2009.

Vectibix® Prescribing Information, Amgen Inc. Thousand Oaks, CA; 2009.
 1st-line panitumumab in combination with
chemotherapy: the phase 2 experience

• Feasibility phase 2 design

– Part 1: panitumumab + bolus 5-FU (IFL)
– Part 2: panitumumab + infusional 5-FU (FOLFIRI)

• Tolerabilty (grade 3-4 diarrhoea) as primary endpoint

• 11/19 (58%) in part 1 experienced grade 3-4 diarrhoea

• 6/24 (25%) in part 2 experienced grade 3-4 diarrhoea

Berlin J, et al. Clin Colorectal Cancer 2007;6:427-32.

 1st-line panitumumab in combination with
chemotherapy: phase 2 results

PFS OS RR
Therapy N
(months) (months) (%)

Pmab + IFL 19 5.6 17 47

Pmab + FOLFIRI 24 10.9 22.5 33

Berlin J, et al. Clin Colorectal Cancer 2007;6:427-32.

 Phase 2 trial of panitumumab with FOLFIRI
as 1st-line treatment of patients with
metastatic colorectal cancer
E
S
N
A
D
F E
E E N
S O
N T D
C F
R Y
R O
O
Previously E Panitumumab T
L F F
untreated mCRC E (6 mg/kg IV on day 1 of each cycle) R
L O
patients N plus FOLFIRI E
M L S
I A
E L T
N Cycles repeated
N every 14 days T
G O U
T M
W D
E
Within Day 1* Y
28 days
N
prior to U
day 1
T
P
*Day 1= day of first treatment administration

Approx. 56 days
after end of treatment

www.amgentrials.com; protocol ID: 20060314. ClinicalTrials.gov identifier: NCT00508404.

Köhne CH, et al. ASCO-GI 2010, #414, poster presentation.
 Phase 2 trial of 1st-line panitumumab plus FOLFIRI
Primary analysis: selected objectives and endpoints

• Objectives
– To estimate the effect of KRAS mutation status on
objective response rate and other measures of efficacy
for 1st-line treatment of mCRC patients with
panitumumab plus FOLFIRI
– To describe the safety profile of this combination
therapy in the 1st-line setting

• Study endpoints: – Secondary endpoints include:

– Primary: - Disease control rate
- Objective response rate - Progression-free survival
- Safety

Köhne CH, et al. ASCO-GI 2010, #414, poster presentation.

 Phase 2 trial of 1st-line panitumumab plus
FOLFIRI KRAS mutation status

• At the time of primary analysis (June 2009) KRAS evaluable

samples were available for 145 of a total of 154 patients
(94%)
– 86 patients (59%) with KRAS WT tumours
– 59 patients (41%) with KRAS MT tumours

• DNA was isolated from paraffin-embedded tissue or

unstained tumour slides from primary or metastatic
tumour*
• Central KRAS testing was performed at HistoGeneX,
Belgium, with a research-use-only DxS Test Kit that used
allele-specific, real-time polymerase chain reaction (PCR)
– The kit can detect approximately 1% of mutant DNA in a
background of wild-type genomic DNA

*Greil R, et al. J Clin Oncol 2009;27(15S):4085;

Köhne CH, et al. ASCO-GI 2010, #414, poster presentation.
Phase 2 trial of 1st-line panitumumab plus FOLFIRI
Best objective response
Panitumumab + FOLFIRI
Overall* KRAS WT KRAS MT
(N=152) (N=85) (N=58)
Objective response, %
Complete response (CR) 2 2 2
Partial response (PR) 47 54 36
Stable disease (SD) 41 34 52
Disease progression 7 7 7
Unevaluable 1 0 2
Not done 2 2 2
CR + PR,% 49.3 56.5 37.9
(95% CI) (41.1 - 57.6) (45.3 - 67.2) (25.5 - 51.6)
Difference, % N/A 18.54
(95% CI) (0.84, 34.63)

Unadjusted common treatment N/A 2.12

odds ratio (1.02, 4.45)
(95% CI)

*Two patients did not have measurable disease per RECIST guidelines at baseline and were therefore not included in the
analysis of response rate. N/A = not applicable; Disease control rate = CR + PR + SD

Köhne CH, et al. ASCO-GI 2010, #414, poster presentation.

Phase 2 trial of 1st-line panitumumab plus FOLFIRI
Resection rate

20
Resection rate (%)

10
15

7
0
KRAS WT KRAS MT
(N=85) (N=58)

• Resection rates were 15% (95%CI: 8.3% to 24.5%) and 7% (95% CI: 1.9% to
16.5%) in the KRAS WT and MT groups, respectively

Köhne CH, et al. ASCO-GI 2010, #414, poster presentation.

 Progression-free survival
KRAS tumour response analysis set

Events Median
100 N (%) (95% CI) months
KRAS WT (N=86) 44 (51) 8.9 (7.6 - 14.3)
90
Proportion Event-Free (%)

KRAS MT (N=59) 48 (81) 7.2 (5.6 - 7.8)

80
HR=0.46 (95% CI: 0.31 - 0.70)
70
60
50
40
30
20
10
0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
Patients
at risk:
Months
WT 86 85 78 76 71 65 54 51 32 25 22 16 11 8 5 1 0
MT 59 58 53 53 46 40 30 25 16 14 8 7 3 2 0 0 0

Köhne CH, et al. ASCO-GI 2010, #414, poster presentation.

 Grade 3/4 adverse events of interest
KRAS safety analysis set
Panitumumab + FOLFIRI (N=145)
Adverse event by MedDRA1, N(%) KRAS WT (N=86) KRAS MT (N=59)
Patients with any event 63 (73) 42 (71)
Skin toxicity 25 (29) 19 (32)
Diarrhoea 20 (23) 13 (22)
Neutropenia 14 (16) 12 (20)
Pulmonary embolism 6 (7) 6 (10)
Paronychia 6 (7) 2 (3)
Dehydration 4 (5) 2 (3)
Stomatits 4 (5) 2 (3)
Hypomagnesaemia 4 (5) 1 (2)
Febrile neutropenia 1 (1) 0 (0)
Infusion-related reaction (panitumumab) 0 (0) 0 (0)
Fatal adverse events2 7 (8) 6 (10)
1MedDRA = Medical Dictionary for Regulatory Activities;
2Includes cases in which primary cause of death was reported to be disease progression; 3 were reported to
be related to panitumumab: haematemesis (WT), rectal haemorrhage (WT) and vena cava thrombosis (MT)

Köhne CH, et al. ASCO-GI 2010, #414, poster presentation.

Phase 2 trial of 1st-line panitumumab plus FOLFIRI
Conclusions
• Panitumumab combined with FOLFIRI appears to be a well-
tolerated regimen in the 1st-line setting

• The results of these exploratory analyses comparing

patients with KRAS WT and MT tumours suggest that KRAS
status is predictive of outcome in this setting

– PFS appears to be longer in patients with KRAS WT

tumours (HR=0.46; 95% CI: 0.31-0.70)

– KRAS WT tumours were more likely to respond to

treatment with panitumumab plus FOLFIRI (OR 2.12;
95% CI: 1.02–4.45)

– Resection rate was higher in the KRAS WT population

(15%) than in the KRAS MT population (7%)
Köhne CH, et al. ASCO-GI 2010, #414, poster presentation.
 Randomised phase 3 study of panitumumab
with FOLFOX4 vs FOLFOX4 alone as 1st-line
treatment in patients with mCRC:
the PRIME trial
J.Y. Douillard,1 S. Siena,2 J. Cassidy,3
J. Tabernero,4 R. Burkes,5 M.E. Barugel,6 Y. Humblet,7
D. Cunningham,8 M. Wolf,9 J. Gansert9

1Centre
René Gauducheau, Nantes, France; 2Ospedale Niguarda Ca’ Granda, Milan, Italy;
3The Beatson West Of Scotland Cancer Centre, Glasgow, United Kingdom; 4Vall d'Hebron

University Hospital, Barcelona, Spain; 5Mount Sinai Hospital, Toronto, Canada; 6Hospital de
Gastroenterología, Buenos Aires, Argentina; 7Centre du Cancer de l'Université Catholique de
Louvain, Brussels, Belgium; 8The Royal Marsden NHS Foundation Trust, London, United
Kingdom; 9Amgen Inc., Thousand Oaks, California

NCT00364013; Amgen 20050203.

Douillard JY, et al. Eur J Cancer 2009; 7(3S):6.10LBA, oral presentation.
 The PRIME trial

• PRIME is an open-label, randomised, global,

phase 3 trial prospectively investigating
panitumumab with FOLFOX4 vs. FOLFOX4 alone
as 1st-line treatment for mCRC among patients
with WT KRAS tumours

• Originally designed to compare the treatment

effect in the all randomised population, the trial
was amended to focus on hypothesis testing in
the WT KRAS subset

NCT00364013; Amgen 20050203.

Douillard JY, et al. Eur J Cancer 2009; 7(3S):6.10LBA, oral presentation.
 Study schema and stratification
E L
N O
S E Tx Arm 1: D N
C N G
R Panitumumab
R O T
O 6.0 mg/kg Q2W + Canada
E F E
L FOLFOX4 Q2W R
E T
L M
N R Mexico
I M E F Costa
E Tx Arm 2: A O
N Rica
T L
G N FOLFOX4 Q2W M L
T E O
South
Disease assessment N W PRIME Australia
T
Africa
every 8 weeks U Study
P Countries Brazil United Kingdom
Chile Belgium
Argentina France
Enrollment Target: Spain
1150 patients Switzerland
Italy
Poland
Randomization stratification: Czech Republic
• ECOG score: 0-1 vs. 2 Hungary
Latvia
• Geographic Region: Western
Europe, Canada, and Australia
vs. Rest of the World

NCT00364013; Amgen 20050203.

Douillard JY, et al. Eur J Cancer 2009; 7(3S):6.10LBA, oral presentation.
 PRIME study timeline
Final
Protocol Primary SAP
Amendment Amendment
10 Oct 2007 10 Dec 2008

First Patient KRAS

Enrolled Last Patient
Enrolled Testing
23 Aug 2006 Completed
1 Feb 2008
Mar 2009

2006 2007 2008 2009

KRAS SEQUENCE
ANALYSIS
(Selected Samples from
Study
CRC Phase 2 Studies) Unblinding
and Primary
20020408 Analysis
KRAS 31 July 2009
ANALYSIS

NCT00364013; Amgen 20050203.

Douillard JY, et al. Eur J Cancer 2009; 7(3S):6.10LBA, oral presentation. SAP = Statistical analysis plan
 Study objective and endpoints
• Primary objective:
– To assess the effect of panitumumab on progression-
free survival (PFS) by KRAS status*

• Primary endpoint:
– PFS (by blinded central radiology review)

• Other key endpoints:

– Overall survival (OS)
– Objective response rate (ORR)
– Time-to-response (TTR)
– Duration of response (DOR)
– Safety *KRAS status was determined by blinded, independent central testing

NCT00364013; Amgen 20050203.

Douillard JY, et al. Eur J Cancer 2009; 7(3S):6.10LBA, oral presentation.
 Key eligibility criteria
• Metastatic adenocarcinoma of the colon or rectum
• No prior treatment for mCRC
– Adjuvant 5-FU-based therapy was allowed if disease
progression occurred >6 months after completion
– Prior oxaliplatin was not allowed
• No prior EGFR inhibitor therapy
• Measurable disease
• Paraffin-embedded tumour tissue available for central biomarker
testing
– EGFR expression and KRAS status were not required at entry
• ECOG performance status 0-2
• Adequate haematologic, renal and hepatic function
• Signed informed consent

NCT00364013; Amgen 20050203.

Douillard JY, et al. Eur J Cancer 2009; 7(3S):6.10LBA, oral presentation.
 Statistical considerations
PFS, WT KRAS
• Sample size calculation for PFS α=0.05

ƒ 380 events in WT KRAS stratum

ƒ 90% power for the WT patients p>0.05
(Hazard Ratio [HR] = 0.71) STOP

ƒ 1150 patients planned p≤0.05

OS, WT KRAS PFS, MT KRAS

• Interim analyses for OS using α=0.05 α=0.05
Haybittle-Peto boundaries, α = 0.001
p>0.05
STOP
• This trial was overseen by an
independent DMC p≤0.05

OS, MT KRAS
α=0.05

NCT00364013; Amgen 20050203.

Douillard JY, et al. Eur J Cancer 2009; 7(3S):6.10LBA, oral presentation.
 Treatment assignment by KRAS status
SCREENED FOR ELIGIBILITY (N=1378)

EXCLUDED (DID NOT

MEET INCLUSION
CRITERIA (N=195)
PATIENTS RANDOMIZED (N =1183)

PANITUMUMAB 6.0 mg/kg

FOLFOX4
+ FOLFOX4
(N=590)
(N=593)

TUMOR SAMPLE TUMOR SAMPLE

AVAILABLE AND AVAILABLE AND
KRAS TESTING KRAS TESTING
COMPLETED (N=546) COMPLETED (N = 550)

KRAS WT KRAS MT
PANITUMUMAB PANITUMUMAB KRAS WT KRAS MT
+ FOLFOX4 + FOLFOX4 FOLFOX4 FOLFOX4
(N=325) (N=221) (N=331) (N=219)

NCT00364013; Amgen 20050203.

Douillard JY, et al. Eur J Cancer 2009; 7(3S):6.10LBA, oral presentation.
 Results: KRAS ascertainment
Panitumumab
+ FOLFOX4 FOLFOX4 Total
Patients randomized, N 593 590 1183

Patients included in KRAS analysis – % 92 93 93

WT KRAS – % 60 60 60

MT KRAS – % 40 40 40

Patients with KRAS unevaluable, % 8 7 7

KRAS tumour status was determined using the DxS kit (Manchester, UK)
that tests the 7 most common KRAS mutations in codons 12 and 13.

NCT00364013; Amgen 20050203.

Douillard JY, et al. Eur J Cancer 2009; 7(3S):6.10LBA, oral presentation.
 Demographics and disease characteristics
WT KRAS MT KRAS
Panitumumab Panitumumab
+ FOLFOX4 FOLFOX4 + FOLFOX4 FOLFOX4
(N=325) (N=331) (N=221) (N=219)
Sex – Men, % 67 62 66 58
Age – years, median (min, max) 62 (27, 85) 61 (24, 82) 63 (33, 83) 61 (27, 82)
Race – White, % 91 93 89 89
ECOG performance status, %
0-1 94 94 96 96
2a 6 5 4 4a
Region, %
Western EU, Canada, Australia 60 56 54 56
Primary Diagnosis, %
Colon cancer 66 65 68 73
Rectal cancer 34 35 32 27
Prior adjuvant, % 16 17 16 12
Sites of metastatic disease, %
Liver only 18 17 14 16
Liver + other sites 69 69 71 73
Median follow-up time, weeks 57 54 47 52

NCT00364013; Amgen 20050203. a Includes 1 patient with ECOG 4

Douillard JY, et al. Eur J Cancer 2009; 7(3S):6.10LBA, oral presentation.
 WT KRAS: progression-free survival
Events Median
N (%) (95% CI) months
100% Panitumumab + 199 (61) 9.6 (9.2 - 11.1)
FOLFOX4
90%
FOLFOX4 215 (65) 8.0 (7.5 - 9.3)
Proportion Event-Free

80%

70%
HR=0.80 (95% CI: 0.66 - 0.97)
60% p=0.02

50%

40%

30%

20%

10%

0%
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23

Months
Patients at risk:
Panitumumab+FOLFOX4 325 313 294 284 254 243 204 187 156 145 111 94 73 57 39 28 22 14 10 4 1 0 0 0
FOLFOX4 alone 331 321 296 281 242 231 185 172 127 113 82 65 41 36 29 22 16 12 10 2 1 1 1 0

NCT00364013; Amgen 20050203.

Douillard JY, et al. Eur J Cancer 2009; 7(3S):6.10LBA, oral presentation.
 WT KRAS: subgroup analyses for PFS
Factors N Favours: pmab no pmab HR 95% CI

All randomized 656 0.80 0.66-0.97

Primary: colon 430 0.79 0.62-1.00
Primary: rectal 226 0.83 0.59-1.16
Liver mets: yes 566 0.78 0.64-0.96
Liver mets: no 90 0.91 0.54-1.54
Liver mets only: yes 116 0.82 0.50-1.34
Liver mets only: no 540 0.81 0.65-1.00
Met sites: <3 363 0.85 0.65-1.11
Met sites: ≥3 290 0.76 0.57-1.02
ECOG: 0 369 0.68 0.52-0.90
ECOG: 1 248 0.92 0.68-1.24
ECOG: 2 38 1.99 0.96-4.15
Age ≥65 261 1.02 0.75-1.38
Age <65 395 0.70 0.54-0.89
Men 421 0.71 0.55-0.90
Women 235 1.00 0.73-1.39

0.10 1.00 10.00

Hazard ratio (pmab / no pmab)

NCT00364013; Amgen 20050203.

Douillard JY, et al. Eur J Cancer 2009; 7(3S):6.10LBA, oral presentation.
 KRAS WT: trend for longer overall survival
(Secondary endpoint)
Events Median
N (%) (95% CI) months
100%
Panitumumab + 165 (51) 23.9 (20.3 - 28.3)
90% FOLFOX4
FOLFOX4 190 (57) 19.7 (17.6 - 22.6)
80%

70% HR=0.83 (95% CI: 0.67 - 1.02)

Survival Probability

p=0.07
60%

50%

40%

30%

20%

10%

0
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36
Months

Patients at risk:
Panitumumab
+FOLFOX4 325 315 310 288 266 242 227 217 207 189 164 135 104 74 55 29 9 2 0
FOLFOX4 alone 331 320 301 281 265 242 223 207 188 170 145 116 77 56 36 21 9 3 0

Siena S, et al. ASCO-GI 2010, #283, oral presentation.

 KRAS WT: subgroup analyses for OS
Factors N Favours: pmab no pmab HR 95% CI

All randomized 656 0.83 0.67-1.02

Primary: colon 430 0.82 0.64-1.05
Primary: rectal 226 0.77 0.53-1.12
Liver mets: yes 566 0.77 0.61-0.96
Liver mets: no 90 1.12 0.65-1.91
Liver mets only: yes 116 0.93 0.51-1.69
Liver mets only: no 540 0.79 0.63-0.99
Met sites: <3 363 0.88 0.65-1.17
Met sites: ≥3 290 0.71 0.53-0.96
ECOG: 0 369 0.72 0.53-0.98
ECOG: 1 248 0.89 0.65-1.22
ECOG: ≥2 38 1.46 0.73-2.92
Age ≥65 261 0.81 0.59-1.11
Age <65 395 0.80 0.61-1.06
Men 421 0.77 0.59-1.00
Women 235 0.88 0.62-1.24

0.10 1.00 10.00

Hazard ratio (pmab / no pmab)

Siena S, et al. ASCO-GI 2010, #283, oral presentation.

 WT KRAS: objective response
Central Review
Panitumumab
+ FOLFOX4 FOLFOX4
(N=317) (N=323)
Objective response rate, 55 48
(50 – 61) (42 – 53)
% (95% CI)*
Complete response 0 0.3

Partial response 55 47

Stable disease 30 36

Progressive disease 7 11

*P = 0.068 (descriptive)

All responses were confirmed no earlier than 28 days after

the response criteria were first met

NCT00364013; Amgen 20050203.

Douillard JY, et al. Eur J Cancer 2009; 7(3S):6.10LBA, oral presentation.
 KRAS WT: significant improvement of PFS
KRAS MT: significant detrimental effect on PFS

100% 100%
KRAS WT KRAS MT
90% 90%
80% 80%
Proportion Event-Free

Proportion Event-Free
70% 70%
60% 60%
50% 50%
40% 40%
30% 30%
20% 20%
10% 10%
0% 0%
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23

Months Months

Events Median Events Median

N (%) (95% CI) months N (%) (95% CI) months
Panitumumab + 199 (61) 9.6 (9.2 - 11.1) Panitumumab + 167 (76) 7.3 (6.3 - 8.0)
FOLFOX4 FOLFOX4
FOLFOX4 215 (65) 8.0 (7.5 - 9.3) FOLFOX4 157 (72) 8.8 (7.7 - 9.4)

HR=0.80 (95% CI: 0.66 - 0.97) HR=1.29 (95% CI: 1.04 - 1.62)
p=0.02 p=0.02

NCT00364013; Amgen 20050203.

Douillard JY, et al. Eur J Cancer 2009; 7(3S):6.10LBA, oral presentation.
 Trends for OS benefit in KRAS WT patients
and detrimental effect in KRAS MT patients
100% 100%

90%
KRAS WT 90%
KRAS MT
80%

Survival Probability
Survival Probability

80%
70% 70%
60% 60%

50% 50%
40% 40%

30% 30%
20% 20%
10% 10%
0 0
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36

Months Months

Events Median Events Median

N (%) (95% CI) months N (%) (95% CI) months
Panitumumab+ 165 (51) 23.9 (20.3 - 28.3) Panitumumab+ 152 (69) 15.5 (13.1 - 17.6)
FOLFOX4 FOLFOX4
FOLFOX4 190 (57) 19.7 (17.6 - 22.6) FOLFOX4 142 (65) 19.3 (16.5 - 21.8)

HR=0.83 (95% CI: 0.67 - 1.02) HR=1.24 (95% CI: 0.98 - 1.57)
p=0.07 p=0.07

Median actual follow-up time (data cut-off 28 August 2009): 20 months pmab + FOLFOX4 and 17 months FOLFOX4
(KRAS wt), 14 months pmab + FOLFOX4 and 16 months FOLFOX4 (KRAS MT)
A pre-specified descriptive final analysis of OS is planned after a 2.5 year minimum follow-up period

Siena S, et al. ASCO-GI 2010, #283, oral presentation.

 MT KRAS: objective response

Central Review
Panitumumab
+ FOLFOX4 FOLFOX4
(N=215) (N=211)
Objective tumor response, % 40 40
(95% CI)* (33 - 46) (34 - 47)
Complete response 0 0
Partial response 40 40
Stable disease 38 43
Progressive disease 13 11

*P = 0.98 (descriptive) All responses were confirmed no earlier than 28

days after the response criteria were first met
NCT00364013; Amgen 20050203.
Douillard JY, et al. Eur J Cancer 2009; 7(3S):6.10LBA, oral presentation.
 Treatment exposure
Wild-type KRAS Mutant KRAS
Panitumumab + Panitumumab +
FOLFOX4 FOLFOX4 FOLFOX4 FOLFOX4
(N=322) (N=327) (N=217) (N=218)
Median number of cycles received
Panitumumab 11 - 10 -
Oxaliplatin 11 11 11 11
5-FU (bolus) 12 12 12 12
5-FU (continuous infusion) 12 12 12 12

Relative dose intensity - %

Panitumumab 81 - 83 -
Oxaliplatin 77 79 80 80
5-FU (bolus) 77 81 80 81
5-FU (continuous infusion) 78 81 81 81

Median cumulative total dose

Panitumumab - mg/kg 62 - 57 -
Oxaliplatin – mg/m2 859 865 824 856
5-FU (bolus) – mg/m2 8627 8618 8294 8711
5-FU (continuous infusion) – mg/m2 13483 13229 12878 13109

NCT00364013; Amgen 20050203.

Douillard JY, et al. Eur J Cancer 2009; 7(3S):6.10LBA, oral presentation.
 Grade 3/4 adverse events of interest
WT KRAS MT KRAS
Pmab + Pmab +
Adverse Event by MedDRAa - % FOLFOX4 FOLFOX4 FOLFOX4 FOLFOX4
(N=322) (N=327) (N=217) (N=218)
Patients with any event 84 69 80 73
Skin toxicity 36 2 30 1
Neutropenia 42 41 37 47
Diarrhea 18 9 20 10
Neurologic toxicity 16 16 16 17
Stomatitis 9 1 6 3
Hypomagnesemia 6 0 6 <1
Paronychia 3 0 2 0
Pulmonary embolismb 3 2 3 4
Febrile neutropeniac 2 2 3 3
Infusion-related reaction
(panitumumab) <1 - <1 -

Fatal adverse events 5 6 8 3

aMedDRA = Medical Dictionary for Regulatory Activities,

bThere were 2 grade 5 pulmonary embolism in the panitumumab arm
NCT00364013; Amgen 20050203. (1 each in the WT and MT KRAS group)
cThere was 1 grade 5 febrile neutropenia in the panitumumab arm
Douillard JY, et al. Eur J Cancer 2009; 7(3S):6.10LBA, oral presentation. (MT KRAS group)
 PRIME conclusions
• In patients with WT KRAS tumours, panitumumab significantly improved
PFS when added to FOLFOX4
– median 9.6 vs 8.0 mo
– HR=0.80, p=0.02

• RR was improved in patients with WT KRAS tumours (55% vs 48%)

• Interim OS was improved in patients with WT KRAS tumours

– median 23.9 vs 19.7 mo
– HR=0.83, p=0.07
– Additional follow-up is required

• In patients with MT KRAS tumours, outcomes were inferior for

panitumumab + FOLFOX4 vs FOLFOX4 alone
– Mechanism unknown

• Panitumumab was well-tolerated when administered with FOLFOX4

– The AE profile was as expected for an anti-EGFR antibody
– Grade 3/4 panitumumab-related infusion reactions were rare (N=2/539)

Siena S, et al. ASCO-GI 2010, #283, oral presentation; Douillard JY, et al. Eur J Cancer 2009; 7(3S):6.10LBA, oral presentation.
 Overall conclusions
• In 1st-line treatment of mCRC, KRAS status was
predictive of efficacy of panitumumab in combination
with
– FOLFOX4 (PRIME) or
– FOLFIRI (phase 2 studies)

• In patients with KRAS WT tumours, the PRIME study

showed a significant PFS advantage and non-
significant benefits in OS and ORR for the addition of
panitumumab to chemotherapy

• Panitumumab in combination with chemotherapy

(FOLFOX4 or FOLFIRI) had a favourable safety profile,
in line with other studies of anti-EGFR mAbs in similar
settings
Siena S, et al. ASCO-GI 2010, #283, oral presentation; Douillard JY, et al. Eur J Cancer 2009; 7(3S):6.10LBA, oral presentation;
Köhne CH, et al. ASCO-GI 2010, #414, poster presentation.