Randomized phase III study of panitumumab (pmab) with FOLFOX4 compared to FOLFOX4 alone as first-line treatment (tx) for metastatic colorectal cancer (mCRC): PRIME trial analysis by epidermal growth factor receptor (EGFR) tumor staining.

Abstract

3566^ Background: This study evaluated the efficacy and safety of pmab + FOLFOX4 versus FOLFOX4 alone as first-line tx for mCRC by tumor KRAS status; analyses by EGFR staining were also performed. Methods: Pts who received no prior chemotherapy for mCRC and no prior oxaliplatin were randomized 1:1 to pmab 6.0 mg/kg Q2W+FOLFOX4 (Arm 1) or FOLFOX4 alone (Arm 2). The primary endpoint was progression-free survival (PFS); overall survival (OS) was secondary. PFS and OS were prospectively analyzed according to KRAS status. Using the Dako EGFR pharmDx immunohistochemistry kit, tumor tissue sectioned within 2 months prior to testing was evaluated for EGFR staining. EGFR results were not required for study entry. Results: 1,183 pts were randomized. Demographics and baseline characteristics were generally balanced. 1,096 pts (93%) had KRAS results. For WT KRAS, median PFS was 9.6 mos for Arm 1 and 8.0 mos for Arm 2; median OS was 23.9 mos for Arm 1 and 19.7 mos for Arm 2. 813 (69%) pts had EGFR results. The most common reason for no EGFR result was tissue section ≥2 months old. Of 479 WT KRAS pts with EGFR results, 326 (68%) were EGFR+. The Table shows the treatment effect within the subpopulations by EGFR staining. No treatment effect by EGFR staining was observed in a stratified multivariate Cox model evaluating the predictive effect of EGFR parameters on PFS (p = 0.89) and OS (p = 0.43) in KRAS WT pts. Except for known toxicities associated with anti-EGFR tx adverse event rates were generally comparable across arms. Conclusions: When added to FOLFOX for first-line mCRC tx, pmab significantly improves PFS and is well tolerated in pts with WT KRAS. A consistent effect of pmab on PFS and OS was observed in both EGFR+ and EGFR- subsets. Further results by EGFR staining parameters will be presented. Efficacy by EGFR membrane staining-WT KRAS WT KRAS N = 656 EGFR evaluable WT KRAS N = 479 HR (95% CI) p value HR (95% CI) EGFR+ HR (95% CI) EGFR- PFS* 0.80 0.77 0.80 Pmab FOLFOX : FOLFOX (0.66-0.97) 0.02 (0.58-1.03) (0.53-1.21) OS 0.83 0.77 0.64 Pmab FOLFOX : FOLFOX (0.67- 1.02) 0.07 (0.52-1.13) (0.34-1.18) * By blinded central review. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen Amgen, AstraZeneca, Celgene, Fresenius Biotech, Merck Serono, Roche, sanofi-aventis Amgen Amgen, Merck AG, Merck Serono, sanofiaventis Amgen, Merck AG, Merck Serono, Pfizer 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.