Citation: European Journal of Cancer Supplements, Vol. 7, No 3, September 2009, Page 6

J. Douillard¹, S. Siena², J. Cassidy³, J. Tabernero⁴, R. Burkes⁵, M.E. Barugel⁶, Y. Humblet⁷, D. Cunningham⁸, M. Wolf⁹, J.L. Gansert<sup>9

1</sup>Centre Rene Gauducheau, Site Hospitalier Nord, Nantes-Saint-Herblain, France
²Ospedale Niguarda Ca' Granda, SC Divisione Oncologia Falck, Milan, Italy
³Cancer resarch UK, department of Oncology, Glasgow University, Glasgow, UK
⁴Vall d'Hebron University Hospital, Medical Oncology Department, Barcelona, Spain
⁵Mount Sinai Hospital, Oncology Department, Toronto, Canada
⁶Hospital de Gastroenterologia, Medical Oncology, Buenos Aires, Argentina
⁷Universite Catholique De Louvain, Centre du Cancer, Brussels, Belgium
⁸The Royal marsden, NHS Foundation Trust, London, United Kingdom
⁹Amgen Inc., Biostatistics, Thousand Oaks CA, USA

Background: Panitumumab (pmab) is a fully human anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) approved as monotherapy for patients (pts) with mCRC. The PRIME trial was designed to evaluate the efficacy and safety of pmab with FOLFOX4 vs FOLFOX4 alone as 1st-line tx for mCRC (clinicaltrials.gov identifier: NCT00364013; sponsor: Amgen Inc).
Methods: This was a randomized, multicenter, phase 3 study. Pts were randomized 1:1 to receive pmab 6.0 mg/kg Q2W + FOLFOX4 (Arm 1) vs FOLFOX4 (Arm 2). Pts had metastatic adenocarcinoma of the colon or rectum; no prior chemotherapy for mCRC; no prior oxaliplatin; ECOG 0–2; and available tumor tissue for biomarker testing. Randomization was stratified by ECOG 0–1 vs 2 and region. The primary endpoint was progression-free survival (PFS). Originally designed to compare the tx effect in the all randomized population, the study was amended to focus hypothesis testing in the wild-type (WT) KRAS subset. KRAS status was determined by a blinded central laboratory using allele-specific PCR prior to the primary analysis.
Results: From Aug 2006 to Feb 2008, a total of 1,183 pts were randomized after signing an informed consent, and received tx: 593 Arm 1, 590 Arm 2. Demographics were generally well-balanced and included 63% men, median age 62 years [range: 24–85]; ECOG 0 or 1; 95%. 1096/1183 pts (93%) had KRAS results: 656 (60%) WT, 440 (40%) mutant (MT). For pts with WT KRAS, median PFS was 9.6 months for Arm 1 and 8.0 months for Arm 2; HR (95% CI) = 0.80 (0.66, 0.97); p = 0.0234 and response rate (by blinded central review) was 55% (Arm 1) and 48% (Arm 2). For pts with MT KRAS, median PFS was 7.3 months for Arm 1 and 8.8 months for Arm 2; HR (95% CI) = 1.29 (1.04, 1.62); p = 0.0227. Adverse event rates were comparable across arms with the exception of known toxicities associated with anti-EGFR therapy such as rash, diarrhea, and hypomagnesemia. Pmab-related grade 3 infusion reactions were reported for 2 patients in Arm 1 (<1%).
Conclusions: Pmab significantly improves PFS and is well tolerated when added to FOLFOX4 for 1st-line tx of pts with WT KRAS mCRC. PFS was inferior in the pts with MT KRAS tumors who received pmab. This study confirms the importance of KRAS as a predictive biomarker in the setting of 1^st-line mCRC tx with an anti-EGFR mAb in combination with chemotherapy.

Presidential session V
Reprinted with permission. © 2009 American Society of Clinical Oncology. All rights reserved. www.Cancer.Net
Thursday 24 September 2009, 12.30–14.30