1. ASCO 2011 A. Sobrero, 1 M. Peeters, 2 T. Price, 3 Y. Hotko, 4 A. Cervantes, 5 M. Ducreux, 6 T. André, 7 E. Chan, 8 F. Lordick 9 Y. Tian, 10 R. Sidhu 10 1 Ospedale San Martino, Genoa, Italy; 2 University Hospital Antwerp, Antwerp, Belgium; 3 Queen Elizabeth Hospital, Woodville, Australia; 4 Uzhgorod National University, Uzhgorod, Ukraine; 5 Hospital Clínico, University of Valencia, Spain; 6 Institut Gustave Roussy, Villejuif, France; 7 Hôpital Pitié-Salpêtrière, Paris, France; 8 Vanderbilt University Medical Center, Nashville, Tennessee; 9 Nationales Centrum für Tumorerkrankungen, Heidelberg, Germany; 10 Amgen Inc., Thousand Oaks, California Final Results from Study 181: Randomized Phase 3 Study of FOLFIRI +/- Panitumumab for the Treatment of 2 nd ‑ line Metastatic Colorectal Cancer

2. GICS 2012 Conflicts of interest This study was funded by Amgen A. Sobrero: consultant/advisory role for Amgen, Merck-Serono and Roche and received honoraria M. Peeters: consultant/advisory role for Amgen and also received honoraria and research funding T. Price: consultant/advisory role for Amgen and received honoraria Y. Hotko: None A. Cervantes: consultant/advisory role for Amgen and also received honoraria M. Ducreux: consultant/advisory role for Amgen and Roche and also received honoraria and research funding T. André: consultant/advisory role for Amgen and Roche and received honoraria E. Chan: consultant/advisory role and received honoraria from Amgen, Genentech, ImClone Systems, Bristol- Myers Squibb and Celgene and research funding from Amgen, ImClone Systems, Pfizer, Roche, Plexxilon, Idera Pharmaceuticals, EMD Serono, Genentech, Bristol- Myers Squibb, and Eli Lilley F. Lordick: received honoraria from Amgen and Merck KGaA and also received research funding from the latter Y. Tian: employed by Amgen R. Sidhu: employed by Amgen

3. GICS 2012 Study Schema and Stratification Randomization stratification: – –ECOG PS: 0-1 vs 2 – –Prior oxaliplatin exposure – –Prior bevacizumab exposure Treatment arm 1: Pmab 6.0 mg/kg Q 2 weeks + FOLFIRI Q 2 weeks ENROLLMENTENROLLMENT END OFTREATMENTEND OFTREATMENT LONG TERMFOLLOWUPLONG TERMFOLLOWUP Disease assessments every 8 weeks Treatment arm 2: FOLFIRI Q 2 weeks SCREENINGSCREENING Enrollment target 1100 patients

4. GICS 2012 Introduction The primary analysis of the 181 trial showed: 1 – –Significantly improved PFS and RR – –A trend towards improved OS Here we present – –A pre-specified descriptive efficacy analysis planned for 30 months after the last patient enrolled (No formal hypothesis testing was planned) – –Efficacy outcomes were analyzed by skin toxicity (ST) Grade (0-1 vs 2-4) to investigate a possible correlation among patients who were alive without PD at day 28 1 Peeters et al. J Clin Oncol 2010; 28: 4706-13

5. GICS 2012 Demographics and Disease Characteristics WT KRAS (n=597) MT KRAS (n=486) Pmab + FOLFIRI (n=303) FOLFIRI (n=294) Pmab + FOLFIRI (n=238) FOLFIRI (n=248) Sex – % male62655660 Median age – years6061 64 Race – % white9795 96 ECOG PS 0-1 – %959394 Prior oxaliplatin therapy – %67656968 Prior bevacizumab therapy – %18201917 Primary colon cancer – %626466 Sites of metastases – % Liver only17201615 Liver plus other68657069 Other only16151416

6. GICS 2012 Objective Response Rate (Central Review) WT KRAS a (n=597)MT KRAS a (n=486) Pmab + FOLFIRI (n=297) FOLFIRI (n=286) Pmab + FOLFIRI (n=232) FOLFIRI (n=248) ORR - % (95% CI)36.0 9.8 13.414.8 Adjusted b odds ratio (95% CI) 5.5 (3.3, 8.9) 0.9 (0.5, 1.0) P-value<0.0001 0.88 All responses were required to be confirmed at least 28 days after the response criteria were first met.

7. GICS 2012 PFS (Central Review) 03691215182124273033363942 Pmab + FOLFIRI (n=303) FOLFIRI alone (n=294) WT 0 20 40 60 80 100 Proportion event free (%) MT Events n (%) Median (95% CI), months Pmab + FOLFIRI283 (93)6.7 (5.8, 7.4) FOLFIRI alone 274 (93)4.9 (3.8, 5.5) Hazard ratio (95% CI): 0.82 (0.69, 0.97) P-value: 0.023 03691215182124273033363942 Pmab + FOLFIRI (n=238) FOLFIRI alone (n=248) 0 20 40 60 80 100 Proportion event free (%) Events n (%) Median (95% CI), months Pmab + FOLFIRI229 (96)5.3 (4.2, 5.7) FOLFIRI alone 237 (96)5.4 (4.0, 5.6) Hazard ratio (95% CI): 0.94 (0.78, 1.14) P-value: 0.56 Months

8. GICS 2012 OS Months Pmab + FOLFIRI (n=303) FOLFIRI alone (n=294) WT 0 20 40 60 80 100 Proportion event free (%) MT Events n (%) Median (95% CI), months Pmab + FOLFIRI267 (88)14.5 (13.0, 16.1) FOLFIRI alone 256 (87)12.5 (11.2, 14.2) Hazard ratio (95% CI): 0.92 (0.78, 1.10) P-value: 0.37 03691215182124273033363942 Months Pmab + FOLFIRI (n=238) FOLFIRI alone (n=248) 0 20 40 60 80 100 Proportion event free (%) Events n (%) Median (95% CI), months Pmab + FOLFIRI221 (93)11.8 (10.4, 13.3) FOLFIRI alone 225 (91)11.1 (10.3, 12.4) Hazard ratio (95% CI): 0.93 (0.77, 1.13) P-value: 0.48 45036912151821242730333639424845

9. GICS 2012 Post-Protocol Treatment WT KRAS (n=597) MT KRAS (n=486) Pmab + FOLFIRI (n=303) FOLFIRI (n=294) Pmab + FOLFIRI (n=238) FOLFIRI (n=248) Subsequent EGFR mAb tx – %1234932 Subsequent chemotherapy – %53504855

10. GICS 2012 Grade 3/4 Adverse Events (AEs) of Interest WT KRAS (n=596)MT KRAS (n=484) AE by MEDRA - % Pmab + FOLFIRI (n=302) FOLFIRI (n=294) Pmab + FOLFIRI (n=237) FOLFIRI (n=247) Skin toxicity 3723231 Neutropenia 20231417 Diarrhea 14 a 91410 Stomatitis/oral mucositis 83104 Hypokalemia 71<10 Pulmonary embolism 5233b3b Dehydration 3232 Hypomagnesemia 3<150 Paronychia 3<130 Febrile neutropenia 23<11 Infusion reactions c 1000 a Includes one Grade 5 AE; b Includes two Grade 5 AEs; c Rates of infusion reactions reported as an AE are shown

11. GICS 2012 Efficacy by ST Grade – WT KRAS ST 2-4 vs FOLFIRI (95% CI): HR=0.72 (0.60, 0.87); p=0.0006 ST 0-1 vs FOLFIRI (95% CI): HR=1.15 (0.89, 1.48); p=0.28 ST 2-4 vs 0.1 (95% CI): HR=0.60 (0.46, 0.80); p=0.0003 ST 2-4 vs FOLFIRI (95% CI): HR=0.80 (0.66, 0.97); p=0.025 ST 0-1 vs FOLFIRI (95% CI): HR=1.48 (1.14, 1.93); p=0.003 ST 2-4 vs 0.1 (95% CI): HR=0.50 (0.38, 0.66); p<0.0001 Events, n (%) 198 (95) 81 (98) 271 (94) Median (95% CI), months 7.4 (6.7, 8.5) 4.0 (3.7, 5.5) 5.1 (3.8, 5.5) FOLFIRI alone Worst ST Grade 2-4 in Pmab arm Worst ST Grade 0-1 in Pmab arm Events, n (%) 187 (90) 76 (92) 254 (88) Median (95% CI), months 16.6 (14.9, 19.4) 8.4 (6.7, 11.3) 12.7 (11.3, 14.3) FOLFIRI alone Worst ST Grade 2-4 in Pmab arm Worst ST Grade 0-1 in Pmab arm Months Worst ST Grade 2-4 in Pmab arm (n=208) Worst ST Grade 0-1 in Pmab arm (n=83) FOLFIRI alone (n=288) PFS 0 20 40 60 80 100 Proportion event free (%) OS Months 0 20 40 60 80 100 Proportion event free (%) 03691215182124273033363942484503691215182124273033363942 Worst ST Grade 2-4 in Pmab arm (n=208) Worst ST Grade 0-1 in Pmab arm (n=83) FOLFIRI alone (n=288)

12. GICS 2012 PRIME: PFS and OS by ST Grade Events n/N (%) Median (95% CI) months Worst ST Grade 2-4 in Pmab arm 157 / 250 (63) 27.7 (23.8 - 30.8) Worst ST Grade 0-1 in Pmab arm50 / 64 (78)11.5 (9.1 - 20.2) FOLFOX4 alone229 / 320 (72) 19.7 (17.6 - 22.7) Grade 2-4 Pmab vs FOLFOX4 HR = 0.75 (95% CI: 0.61 – 0.92) Log-rank p-value = 0.006 WT KRAS and OS ≥ 28 Days Worst Grade ST Grade Events n/N (%) Median (95% CI) months Worst ST Grade 2-4 in Pmab arm 208 / 250 (83)11.3 (9.9 - 13.2) Worst ST Grade 0-1 in Pmab arm55 / 64 (86)6.1 (5.3 - 9.2) FOLFOX4 alone278 / 320 (87)8.7 (7.5 - 9.6) Grade 2-4 Pmab vs FOLFOX4 HR = 0.71 (95% CI: 0.59 – 0.85) Log-rank p-value = 0.0002 WT KRAS and PFS ≥ 28 Days Worst Grade ST Grade

13. GICS 2012 Conclusions Results of the primary analysis confirmed that in K/RAS wt: – –Significantly improved PFS – –Trend towards improved OS – –Significantly improved RR – –No new safety signals One-third of patients in the FOLFIRI alone arm received subsequent anti-EGFR therapy, with potential impact on OS Patients with WT KRAS tumors receiving Pmab + FOLFIRI with Grade 2-4 skin toxicity demonstrated improved PFS and OS, compared with those receiving FOLFIRI alone, or those receiving Pmab + FOLFIRI with Grade 0-1 skin toxicity The inability to mount a skin reaction to anti EGFR seems to be associated with a shorter overall survival

14. GICS 2012 Acknowledgments The authors wish to thank: – –The patients and their families – –The investigators and their study staff worldwide – –The study team at Amgen