Panitumumab (pmab) regimen evaluation in colorectal cancer to estimate primary response to treatment (PRECEPT): Effect of <i>KRAS</i> mutation status on second-line treatment (tx) with pmab and FOLFIRI

Abstract

4127^ Background: Pmab, a fully human antibody to the epidermal growth factor receptor (EGFr), has demonstrated efficacy as monotherapy in patients (pts) with metastatic colorectal cancer (mCRC) after disease progression (PD) on standard chemotherapy (CT). The mutation status of the KRAS gene in tumors has been shown to be a predictive biomarker of response to anti-EGFr antibody monotherapy in mCRC. This study was designed to prospectively estimate the efficacy of FOLFIRI+pmab tx according to tumor KRAS status in patients undergoing second-line tx for mCRC. Methods: 110 pts (as planned) with mCRC with PD after first-line tx with oxaliplatin- based CT+bevacizumab were enrolled in this phase 2, open-label, single-arm trial. Pts had unresectable, measurable disease (per RECIST), ECOG status 0 or 1, and tumor tissue available for KRAS testing. Pts received pmab (6 mg/kg) and FOLFIRI Q2W until PD or intolerability. Tumor assessments were performed at weeks 8, 16, 24, 32, and every 12 weeks thereafter. KRAS mutation status was assessed in extracted DNA from fixed tumor sections using real-time PCR. Safety endpoints included incidence and severity of adverse events (AEs). Efficacy endpoints included objective response rate, progression-free survival (PFS), and overall survival (OS) by KRAS status. Results: At the time of interim data cutoff, 51 pts completed week-16 tumor assessments. Pts received a mean of 6 pmab doses. Pmab-related AEs were seen in 90% of pts. 43 pts (84%) had > grade 3 AEs (related and unrelated to tx). 19 pts (37%) had serious AEs. 7 (14%) pts had partial response (2 confirmed). Conclusions: Pmab/FOLFIRI tx was generally well tolerated and had activity within the expected range in the unselected population. Updated response, PFS, and OS data by KRAS status will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen Inc. Amgen Inc. Amgen Inc., Bristol-Myers Squibb, Genentech