Randomized phase III study of panitumumab (pmab) with FOLFIRI versus FOLFIRI alone as second-line treatment (tx) in patients (pts) with metastatic colorectal cancer (mCRC): Analysis by tumor epidermal growth factor receptor (EGFR) staining.

Abstract

3565^ Background: Pmab, a fully human, anti-EGFR monoclonal antibody, plus FOLFIRI vs FOLFIRI was evaluated as 2nd-line tx for mCRC by tumor KRAS status; efficacy analyses by EGFR staining were also performed. Methods: Pts who received 1 prior chemotherapy tx for mCRC were randomized 1:1 to pmab 6.0 mg/kg Q2W+FOLFIRI (Arm 1) or FOLFIRI (Arm 2). Independently tested coprimary endpoints progression-free survival (PFS) and overall survival (OS) were prospectively analyzed by KRAS status. EGFR+ staining was not required for entry. Tumor tissue must have been sectioned within 2 months prior to testing using the Dako EGFR pharmDx immunohistochemistry kit. Results: 1,186 pts were randomized. Demographics and baseline characteristics were generally balanced. 1,083 pts (91%) had KRAS results and 719 (66%) pts had EGFR results. For WT KRAS, median PFS was 5.9 mos for Arm 1 and 3.9 mos for Arm 2; median OS was 14.5 mos for Arm 1 and 12.5 mos for Arm 2. 391 pts with WT KRAS also had EGFR results; 295 (75%) were EGFR+. The most common reason for no EGFR result was tissue section ≥2 months old. The analysis of treatment effect within the subpopulations by EGFR staining are shown (Table). No treatment effect by EGFR staining was observed in a stratified multivariate Cox model evaluating the predictive effect of EGFR parameters on PFS (p = 0.80) and OS (p = 0.81) in KRAS WT pts. In general, adverse event rates were comparable across arms except for known toxicities associated with anti-EGFR tx. Conclusions: Pmab significantly improves PFS and is well tolerated when added to FOLFIRI for 2nd-line tx in pts with WT KRAS mCRC; a consistent benefit in PFS and OS was observed among EGFR+ as well as EGFR- subsets of patients who received pmab. Further results by EGFR staining parameters will be presented. Efficacy by EGFR membrane staining—WT KRAS WT KRAS N = 597 EGFR evaluable WT KRAS N = 390 HR (95% CI) p value HR (95% CI) EGFR+ HR (95% CI) EGFR− PFS*Pmab FOLFIRI : FOLFIRI 0.73 0.78 0.89 Pmab FOLFIRI : FOLFIRI (0.59-0.90) 0.004 (0.61-1.01) (0.55-1.43) OS 0.85 0.88 0.97 Pmab FOLFIRI : FOLFIRI (0.70-1.04) 0.12 (0.66-1.17) (0.59-1.61) * 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, Lilly, Merck, sanofiaventis Amgen Amgen, Lilly, Merck, Merck Serono, Roche, sanofi-aventis Amgen Amgen Amgen, Lilly, Merck, sanofiaventis 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.