237 - Impact of FCGR2A and FCGR3A Polymorphisms on the Clinical Outcome of Patients With Metastatic Colorectal Cancer Treated With Cetuximab and Folfiri as 2nd-Line Therapy

Abstract

ABSTRACT Background Cetuximab, a chimeric IgG1 anti- EGFR monoclonal antibody shows activity in mCRC, mainly in wild-type KRAS tumors. Recent studies demonstrate antibody-dependent cell-mediated cytotoxicity (ADCC) is one of the modes of action for cetuximab. Fragment c gamma receptors (FcGR) play an important role in initiating ADCC. We investigated the association of FcGR polymorphisms with the outcome of KRAS-wild type mCRC pts treated with cetuximab and FOLFIRI as 2nd line therapy (FLIER study). Patients and methods 60 mCRC pts were enrolled onto the FLIER study, and 56 pts were finally analyzed. Tumor tissues from 56 pts were screened, BRAF and PI3K mutations using direct sequencing and were screened genotype for FcGR2a (H131R) and FcGR3a (V158F) polymorphisms by Taqman assay. The association of each FcGR polymorphism with response rate (RR) and progression free survival (PFS) were analyzed. Results The RR of 56 pts was 33.9%. No patient was response to the regimen with mutated BRAF and PI3K. A statistically significant difference was observed for PFS for F carriers to 158V/V pts (286 vs 154 days; P = 0.047, Kaplan-Meier curves). The difference was more significant among pts without mutation of BRAF or PI3K (301 vs 185 days; P = 0.016). The relationship between RR and polymorphisms was as follows, FcGR2a (HH: 10/35, HR: 6/15, RR: 3/6), FcGR3a (FF: 15/37, FV3/14, VV1/5). There was no relationship between each polymorphisms and RR (Chi-square test). Conclusion In our analysis, mutations such as BRAF and PI3K were also important biomarkers of cetuximab. Furthermore, our date suggest that the FcGR3a polymorphisms may be also useful molecular markers to predict clinical outcome in mCRC pts treated with cetuximab. We will be able to select super-responders to cetuximab in combination with these mutations and FcGR3a polymorphisms. Disclosure All authors have declared no conflicts of interest.