GICS 2012 Final skin toxicity and patient ‑ reported outcomes results from PRIME: A randomized phase 3 study of panitumumab + FOLFOX4 for 1 st ‑ line metastatic colorectal cancer Jean ‑ Yves Douillard, 1 Salvatore Siena, 2 Josep Tabernero, 3 Ronald Burkes, 4 Mario E. Barugel, 5 Yves Humblet, 6 David Cunningham, 7 Feng Xu, 8 Zhongyun Zhao, 8 Roger Sidhu 8 1 Centre René Gauducheau, Nantes, France; 2 Ospedale Niguarda Ca’ Granda, Milan, Italy; 3 Vall d'Hebrón University Hospital, Barcelona, Spain; 4 Mount Sinai Hospital, Toronto, Canada; 5 Hospital de Gastroenterología, Buenos Aires, Argentina; 6 Centre du Cancer de l'Université Catholique de Louvain, Brussels, Belgium; 7 The Royal Marsden NHS Foundation Trust, London, United Kingdom; 8 Amgen Inc., Thousand Oaks, California;

GICS 2012 Introduction Panitumumab is a fully human monoclonal antibody targeting the epidermal growth factor receptor (EGFR) PRIME ( ) was an open-label, randomized, global, phase 3 trial prospectively investigating panitumumab + FOLFOX4 vs FOLFOX4 alone as 1 st - line treatment for metastatic colorectal cancer (mCRC) among patients with wild- type (WT) KRAS tumors The results from the primary analysis of this study showed that panitumumab + FOLFOX4 was generally tolerable and significantly improved progression-free survival (PFS) in patients with WT KRAS mCRC vs FOLFOX4 alone 1 Efficacy and patient-reported outcomes (PRO) by skin toxicity (ST) severity from the final descriptive analysis of PRIME are presented

GICS 2012 Study Schema and Stratification Treatment Arm 1: Panitumumab 6.0-mg/kg Q2W + FOLFOX4 Q2W ENROLLMENTENROLLMENT END OF TREATMENTEND OF TREATMENT LONGTERMFOLLOWUPLONGTERMFOLLOWUP PRO assessments every 4 weeks Disease assessment every 8 weeks Treatment Arm 2: FOLFOX4 Q2W Enrollment target: 1150 patients Randomization stratification: Eastern Cooperative Oncology Group (ECOG) performance status: 0–1 vs 2 Geographic region: Western Europe, Canada, and Australia vs rest of the world Q2W – Every 2 weeks SCREENINGSCREENING PRIME Study Countries Canada Belgium Czech Republic France Hungary Italy Latvia Poland Spain Switzerland United Kingdom South Africa Costa Rica Mexico Argentina Brazil Chile Australia

GICS 2012 Study Objective and Endpoints Primary Objective: – –To assess the effect of panitumumab on PFS by KRAS mutation status* Primary Endpoint: – –PFS (by blinded central radiology review) Other Key Endpoints: – –Overall survival (OS) – –Objective response rate (ORR) – –Time to progression – –Duration of response – –PRO – –Safety *KRAS status was determined by blinded, independent central testing

GICS 2012 Key Eligibility Criteria Metastatic adenocarcinoma of the colon or rectum No prior treatment for mCRC – –Adjuvant 5-fluorouracil-based therapy was allowed if disease recurrence occurred > 6 months after completion – –Prior oxaliplatin was not allowed No prior EGFR inhibitor therapy Measurable disease Paraffin-embedded tumor tissue available for central biomarker testing – –EGFR expression and KRAS status were not required at entry ECOG performance status 0–2 Adequate hematologic, renal, and hepatic function Signed informed consent

GICS 2012 Statistical Considerations for the ST and PRO Analyses The ST and PRO analyses were based on data from the final analysis that occurred 30 months after the last patient was enrolled PRO were assessed using the EuroQol EQ ‑ 5D Health State Index Score and the EQ ‑ 5D Overall Health Rating PRO data were analyzed using a mixed ‑ effect model repeated measure (MMRM) model to analyze longitudinal PRO data with missing values 2,3 All statistical tests were performed at a 2 ‑ sided significance level of 5% without adjusting for multiple comparisons and are regarded as descriptive The primary goal of this analysis was to evaluate the correlation between worst grade ST and efficacy and PRO endpoints The ST analysis includes the primary endpoint of PFS, and secondary endpoints of OS, objective response, and safety Landmark analysis was performed in the efficacy by ST analyses to reduce bias A landmark of day 28 was selected because > 50% of patients had their maximum grade ST by day 28 Patients who were alive without disease progression at day 28 were included in the ST analyses

GICS 2012 Demographics and Disease Characteristics WT KRAS mCRC Panitumumab + FOLFOX4 Grade 2–4 ST (n = 250) Panitumumab + FOLFOX4 Grade 0–1 ST (n = 64) FOLFOX4 (n = 320) Sex, men – n (%)164 (66)43 (67)199 (62) Age – years, median (min, max)61.0 (27, 81)63.5 (30, 80)61.5 (24, 82) Race, white – n (%)227 (91)59 (92)299 (93) ECOG performance status – n (%) 0–1240 (96)58 (91)301 (94) 210 (4)6 (9)18 (6)* Primary tumor type – n (%) Colon cancer162 (65)43 (67)207 (65) Rectal cancer88 (35)21 (33)113 (35) Sites of metastatic disease: Liver only48 (19)11 (17)56 (18) Liver + other174 (70)40 (63)219 (68) Other only28 (11)12 (19)45 (14) Missing or unknown0 (0)1 (2)0 (0) *One patient had missing/unknown ECOG performance status score

GICS 2012 WT KRAS - Final Analysis Events n/N (%) Median (95% CI) months Panitumumab + FOLFOX4 270 / 325 (83) 10.0 (9.3 – 11.4) FOLFOX4280 / 331 (85) 8.6 (7.5 – 9.5) HR = 0.80 (95% CI: 0.67 – 0.95) Log-rank p-value = 0.01 Events n/N (%) Median (95% CI) months Worst ST grade 2-4 in panitumumab arm 208 / 250 (83) 11.3 ( ) Worst ST grade 0-1 in panitumumab arm 55 / 64 (86) 6.1 ( ) FOLFOX4 alone278 / 320 (87) 8.7 ( ) Grade 2-4 panitumumab vs FOLFOX4 HR = 0.71 (95% CI: 0.59 – 0.85) Log-rank p-value = PFS WT KRAS and PFS ≥ 28 Days Worst Grade ST Severity

GICS 2012 Events n/N (%) Median (95% CI) months Panitumumab+ FOLFOX4 214 / 325 (66) 23.9 ( ) FOLFOX4231 / 331 (70) 19.7 ( ) HR = 0.88 (95% CI: 0.73 – 1.06) Log-rank p-value = 0.17 WT KRAS - Final Analysis OS Events n/N (%) Median (95% CI) months Worst ST grade 2-4 in panitumumab arm 157 / 250 (63) 27.7 ( ) Worst ST grade 0-1 in panitumumab arm 50 / 64 (78) 11.5 ( ) FOLFOX4 alone229 / 320 (72) 19.7 ( ) Grade 2-4 panitumumab vs FOLFOX4 HR = 0.75 (95% CI: 0.61 – 0.92) Log-rank p-value = WT KRAS and PFS ≥ 28 Days Worst Grade ST Severity

GICS 2012 Objective Response by Worst Grade ST Severity (Central Review) WT KRAS Panitumumab + FOLFOX4 Grade 2–4 ST (n = 246) a Panitumumab + FOLFOX4 Grade 0–1 ST (n = 61) a FOLFOX4 (n = 313) a ORR – n (%) [95% CI]156 (63) [57 – 69] 25 (41) [29 – 54] 154 (49) [44 – 55] Complete response – n (%)1 (<1)0 (0)2 (<1) Partial response – n (%)155 (63)25 (41)152 (49) Stable disease – n (%)68 (28)23 (38)117 (37) Progressive disease – n (%)14 (6)6 (10)35 (11) Unevaluable or not done – n (%)8 (3)7 (11)7 (2) a Included only patients with baseline measurable disease per central review All responses were required to be confirmed at least 28 days after the response criteria were first met

GICS 2012 PRO Results Summary of EQ-5D Health State Index Score Through Treatment Discontinuation Least Squares Adjusted Mean Difference ([panitumumab + FOLFOX4] – FOLFOX4) (95% CI) Least Squares Adjusted Mean Difference (Grade 0 or 1 – grade ≥ 2 ST) (95% CI) EQ-5D Health State Index Score ( – ) ( – ) EQ-5D Overall Health Rating ( – ) ( – ) The minimal clinically important difference is 0.08 for the EQ-5D Health State Index Score and 7 for the EQ-5D Overall Health Rating 4 Overall Health Rating Change From Baseline Through Disease Progression and Impact of ST on PRO (Central Assessment - WT KRAS PRO Analysis Set)

GICS 2012 Grade 3/4 Adverse Events of Interest by Worst Grade ST Severity WT KRAS mCRC Adverse event by MedDRA Term – n (%) Panitumumab + FOLFOX4 Grade 2–4 ST (n = 250) Panitumumab + FOLFOX4 Grade 0–1 ST (n = 64) FOLFOX4 (n = 320) Patients with any event223 (89) 45 (70)225 (70) Neutropenias116 (46) 21 (33)133 (42) Diarrhea 46 (18)12 (19)28 (9) Neurologic toxicities 48 (19)5 (8)51 (16) Stomatitis/oral mucositis 27 (11)1 (2)2 (<1) Hypokalemia 25 (10)6 (9)15 (5) Fatigue 23 (9)7 (11)10 (3) Hypomagnesemia 18 (7)4 (6)1 (<1) Paronychia 10 (4)1 (2)0 (0) Pulmonary embolism 8 (3)1 (2)5 (2) Febrile neutropenia 5 (2)3 (5)7 (2) Infusion-related reaction (panitumumab) 2 (<1)0 (0)– MedDRA: Medical Dictionary for Regulatory Activities

GICS 2012 Conclusions In the final analysis of PRIME, results from the primary analysis were confirmed: – –Statistically significant improvement in PFS in patients with WT KRAS mCRC receiving panitumumab+FOLFOX4 vs FOLFOX4 alone – –Trend toward improved OS in patients with WT KRAS mCRC receiving panitumumab+FOLFOX4 vs FOLFOX4 alone – –Higher objective response in patients with WT KRAS mCRC receiving panitumumab+FOLFOX4 Patients with WT KRAS mCRC receiving 1 st -line treatment with panitumumab who develop ST grade 2-4 had longer PFS and OS vs patients receiving chemotherapy alone No significant difference in PRO was observed using the EQ-5D instrument in patients with WT KRAS mCRC who received panitumumab+FOLFOX4 that developed high grade 2-4 ST vs low grade 0-1 ST The adverse event profile was as expected for patients receiving anti-EGFR antibodies

GICS 2012 References 1. 1.Douillard JY, et al. J Clin Oncol. 2010;28: Siddiqui O, et al. J Biopharm Stat. 2009;19: Lane P. Pharm Stat. 2008;7: Pickard AS, et al. Health Qual Life Outcomes. 2007;5:70.