Randomized, open-label, phase III study of panitumumab (pmab) with FOLFIRI versus FOLFIRI alone as second-line treatment (tx) in patients (pts) with metastatic colorectal cancer (mCRC): Efficacy by skin toxicity (ST).

Abstract

3529^ Background: Pmab is a fully human anti-epidermal growth factor receptor (EGFR) mAb approved as monotherapy for pts with chemorefractory mCRC. ST is the most common tx-related adverse event (AE). This study evaluated the efficacy and safety of pmab + FOLFIRI vs. FOLFIRI as second-line tx for mCRC by KRAS status; outcomes by ST severity were also evaluated. Methods: Pts were randomized 1:1 to pmab 6.0 mg/kg Q2W + FOLFIRI or FOLFIRI. Pts had metastatic adenocarcinoma of the colon or rectum, 1 prior chemotherapy tx for mCRC, ECOG 0-2. Independently tested co-primary endpoints were progression-free survival (PFS) and overall survival (OS). Results: 1,186 pts were randomized: 591 pmab + FOLFIRI, 595 FOLFIRI. Demographics and baseline characteristics were generally balanced. 1,083 (91%) pts had KRAS results: 597 (55%) wild-type (WT), 486 (45%) mutant (MT). Pmab+FOLFIRI significantly improved PFS in pts with WT KRAS (HR = 0.73; 95% CI:0.59-0.90, p = 0.004; median PFS 5.9 vs 3.9 mos). 93% of pts with WT KRAS and 91% with MT KRAS receiving pmab experienced any ST. Maximum grade (gr) ST was observed by day 28 in > 50% of pts. Pts with at least gr 1 ST who were alive w/o progression at day 28 were included in the ST analysis. In pts with WT KRAS with ST gr 2-4 vs. gr 1, median PFS was 7.4 mos vs. 5.2 mos (HR = 0.67; 95% CI: 0.49-0.90, p = 0.009); median OS was 16.5 mos vs. 10.3 mos (HR = 0.46; 95 CI: 0.33-0.65; p < 0.0001). In pts with MT KRAS, higher ST severity (gr 2-4) was also associated with longer PFS (HR = 0.575; 95% CI: 0.410, 0.805; p = 0.001) and OS (HR = 0.488; 95% CI: 0.340, 0.701, p = 0.0001). AE rates were comparable across arms with the exception of ST and known toxicities associated with anti-EGFR therapy. Conclusions: Pmab + FOLFIRI as second-line tx for mCRC significantly improved PFS in pts with WT KRAS and was well tolerated. In pts with KRAS WT tumors, ST gr 2-4 was associated with longer PFS and OS. Although pts with MT KRAS tumors do not benefit from pmab, a similar association between PFS, OS and ST was seen in these pts. The possible confounding effect of prognosis 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, AstraZeneca, Bayer, Lilly, Merck, Merck Serono, Onyx, Pfizer, Roche, sanofi-aventis Amgen Amgen, AstraZeneca, Bayer, Lilly, Merck, Merck Serono, Onyx, Pfizer, 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.