Randomized, open-label, phase III study of panitumumab (pmab) with FOLFOX4 versus FOLFOX4 alone as first-line treatment (tx) for metastatic colorectal cancer (mCRC): Efficacy by skin toxicity (ST).
Authors: J. Douillard, J. Cassidy, J. Jassem, F. Rivera, I. Kocáková, W. Rogowski, J. R. Canon, E. P. Yanez, F. Xu, J. L. Gansert
Journal: Journal of Clinical Oncology (2010)

3528^ Background: Pmab is a fully human antiepidermal growth factor receptor (EGFR) monoclonal antibody approved as monotherapy for chemorefractory mCRC. ST is the most common anti-EGFR tx-related adverse event (AE). We evaluated the efficacy and safety of pmab+FOLFOX4 vs FOLFOX4 as first-line tx for mCRC; outcomes by tumor KRAS status and ST severity were evaluated. Methods: Pts were randomized 1:1 to pmab 6.0 mg/kg Q2W+FOLFOX4 vs FOLFOX4. Pts had metastatic adenocarcinoma of the colon or rectum, no prior chemotherapy for mCRC, no prior oxaliplatin, ECOG 0-2. The primary endpoint was progression-free survival (PFS); overall survival (OS) was secondary. Results: 1183 pts were randomized: 593 Pmab+FOLFOX4, 590 FOLFOX4. Demographics and disease characteristics were generally balanced. 1,096/1,183 pts (93%) had KRAS results: 656 (60%) wild-type (WT), 440 (40%) mutant (MT). Pmab significantly improved PFS (HR = 0.80; 95% CI: 0.66-0.97; p = 0.02; median 9.6 vs. 8.0 mo) in pts with WT KRAS. 97% of pts with WT KRAS and 95% with MT KRAS tumor status receiving pmab experienced any ST. Maximum grade (gr) ST was observed by day 28 in 50% of pts. Pts with ≥ gr 1 ST who were alive w/o progression at day 28 were included in the ST analysis. For WT KRAS pts with maximum ST gr 2-4 vs. gr 1, median PFS (n = 305) was 10.8 mos vs 6.0 mos (HR = 0.63; 95% CI: 0.42-0.93; p = 0.019), median OS (n = 308) was 28.3 mos vs. 11.5 mos (HR = 0.47; 95 CI: 0.32-0.71; p = 0.0002); in pts with MT KRAS, median PFS (n = 203) was 7.6 mos vs. 5.7 mos (HR = 0.65 [95% CI: 0.45, 0.94] p = 0.022) and median OS (n= 203) was 16.9 mos vs. 10.1 mos (HR = 0.60 [95% CI: 0.41, 0.88] p = 0.009). Except for ST and other known AEs associated with anti-EGFR tx, AEs were comparable across arms. Conclusions: Pmab+FOLFOX4 as first-line tx for mCRC significantly improved PFS in pts with WT KRAS and was well tolerated. ST gr 2-4 vs. 1 was associated with longer PFS and OS in pts with KRAS WT tumors. However, since the same association was seen in pts with MT KRAS who overall do not benefit from pmab, this finding may be confounded with prognostic factors which will be examined. Response rate and patient-reported outcome analyses by ST severity will also be presented. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen, Merck Serono, sanofiaventis Amgen Amgen, Merck Serono, sanofiaventis Amgen In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519-521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2010 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest.