549P - Impact of Tumour Ras/Braf Status on Efficacy of First-Line Panitumumab + Folfiri in Patients (Pts) with Metastatic Colorectal Cancer (Mcrc)

Abstract

ABSTRACT Aim: Data from a phase III study of second-line panitumumab + FOLFIRI treatment showed that RAS mutations beyond those in KRAS exon 2 impact on the risk/benefit profile of panitumumab in pts with mCRC. Here we report a retrospective RAS/BRAF analysis of a mCRC study of first-line panitumumab + FOLFIRI (NCT00508404). Methods: In this phase II, single-arm study, first-line panitumumab (6 mg/kg) + FOLFIRI were administered every 14 days until progression to mCRC pts. Objective response rate (ORR) was the primary endpoint. Data were analysed descriptively by tumour RAS/BRAF status. Tumour specimens were assayed for mutations in KRAS exon 2 by DxS and KRAS exons 3/4, NRAS exons 2/3/4 and BRAF exon 15 by bidirectional Sanger sequencing. Results: RAS data were available for 143/154 (93%) pts of whom 69 (48%) had RAS WT (wild-type [WT] for exons 2, 3 and 4 of KRAS/NRAS) and 74 (52%) had RAS mutant (MT) tumours. Overall, median age was 63 years, 62% had primary colon cancer, 55% had moderately differentiated tumours and 76% had ≤2 metastatic sites. Baseline characteristics were generally well balanced between pts with RAS WT vs MT mCRC. ORRs (59% vs 41%; odds ratio: 2.05; 95% confidence interval [CI]: 0.99-4.23) and resection rates (13% vs 9%) were higher in pts with RAS WT vs MT mCRC. Disease control rates were similar (91% vs 92%; odds ratio: 0.93; 95% CI: 0.23-3.66). Longer median duration of response (DoR: 13.0 vs 5.8 months), progression-free survival (PFS: 11.2 vs 7.3 months) and time to progression (TTP: 13.2 vs 7.3 months) were also observed in RAS WT pts. Nine pts (6%) had BRAF MT mCRC. Pts with RAS/BRAF WT (n = 60) vs RAS WT/BRAF MT (n = 83) status had improved ORR (68% vs 36%; odds ratio: 3.81; 95% CI: 1.78-8.22), resection rates (15% vs 8%), median DoR (13.0 vs 5.8 months), PFS (13.2 vs 6.9 months) and TTP (13.3 vs 7.2 months). No new safety signals were identified. Conclusions: In line with recent studies, consistently favourable efficacy was observed in pts with RAS/BRAF WT vs MT mCRC tumours receiving first-line panitumumab + FOLFIRI treatment. KRAS mutation status appears insufficient for selecting pts for first-line panitumumab + FOLFIRI treatment; tumour RAS analysis aids optimum pt selection. Disclosure: M. Karthaus: Prof Karthaus has participated in Advisory boards (compensated) for Amgen; L. Mineur: has received research support from Amgen (but not in the context of this abstract), honoraria from Amgen for participation in advisory boards (but not for this study); R. Greil: has received honoraria from Amgen for participation in advisory boards and research support from Amgen (but not in the context of this abstract); J. Thaler: has received honoraria and research funding from Amgen; H. Kroning: did not declare any conflicts of interest; K.S. Oliner: is an Amgen Inc. employee and stockholder; J. Terwey: is an Amgen (Europe) GmbH employee and stockholder; All other authors have declared no conflicts of interest.