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RESEARCH PRODUCT

Impact of Baseline Covariates and Prior Therapy on the Efficacy of Second-Line Panitumumab (Pmab) + Folfiri Vs Folfiri Treatment

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ABSTRACT Aim: Expanding RAS analyses beyond KRAS exon 2 is important in selecting patients (pts) for pmab treatment. Here we present prespecified subgroup analyses from a phase 3 randomised second-line pmab + FOLFIRI vs FOLFIRI study in metastatic colorectal cancer (mCRC) pts. Methods: Progression-free (PFS) and overall survival (OS) were co-primary endpoints. KRAS exon 2 wild-type (WT) samples were tested for mutations in KRAS exons 3/4, NRAS exons 2/3/4 and BRAF exon 15 via bidirectional Sanger sequencing and WAVE-based SURVEYOR®. PFS and OS subgroup analyses were performed by randomisation stratification factors (ECOG performance status [PS], prior bevacizumab [bev]/prior oxaliplatin [ox] for mCRC) and prespecified baseline covariates (age, BRAF status). Results: Overall, 18% (107/597) of KRAS exon 2 WT pts had other RAS mutations. In RAS WT pts overall (n = 421), PFS was significantly longer in the pmab + FOLFIRI vs FOLFIRI arm (hazard ratio [HR]: 0.70 [95% confidence intervals {CI}: 0.54-0.91]; p = 0.0069). RAS WT pts Median PFS, months Pmab + FOLFIRI (n = 208) FOLFIRI (n = 213) Age 6.4 4.6 * ≥65 yrs 6.4 3.9 ECOG PS 0/1 6.7 4.6 * 2 3.1 3.5 BRAF MT Yes 2.5 1.8 No 6.9 5.5 * Prior ox Yes 6.1 3.7 * No 6.7 6.9 Prior bev Yes 6.7 3.7 No 6.1 4.6 * * p Conclusions: Consistent PFS benefits were observed across all subgroups in pts with RAS WT mCRC receiving second-line pmab + FOLFIRI vs FOLFIRI alone. Disclosure: M. Peeters: Consultant/advisory roles for Amgen (all compensated) and has also received honoraria and research funding from Amgen; T. Price: Member of advisory boards for Amgen, Roche and Merck Serono (uncompensated); A. Sobrero: Member of advisory boards and speaker at satellite symposia for Celgene, Bayer, Sanofi, Merck, Roche, and Amgen; M.P. Ducreux: Member of advisory boards for Amgen, Merck, Roche, participation in symposium for Amgen, Merck, Roche; T. Andre: Advisory board membership and honoraria from Amgen; C. Punt: Amgen advisory board member; R. Koukakis: Amgen Ltd employee and stockholder;J. Terwey: Amgen (Europe) GmbH employee and stockholder; E. Van Cutsem: Has received research funding from Amgen (paid to University). All other authors have declared no conflicts of interest.