Relationship between Polymorphisms and the Efficacy of Cetuximab]

Cetuximab has shown efficacy in patients with metastatic colorectal cancer(mCRC). Recent studies have demonstrated that cetuximab induces antibody-dependent cell-mediated cytotoxicity(ADCC), mediated via the fragment c gamma receptors(FcgR)in mCRC. Since the establishment of KRAS mutations as a major negative predictor of efficacy, additional biomarkers have been found to be useful for the improvement of selection of patients likely to be responsive to cetuximab. We investigated the relationship between polymorphisms and the outcome of mCRC patients treated with cetuximab.In this study, 57 patients were evaluated. The relationships of FcgR polymorphisms with response rate (RR), progression-free survival(PFS), and overall survival(OS)were analyzed.The FcgR polymorphisms were not significantly related to RR, PFS, and OS. Compared with the other haplotypes, the haplotype containing the 131H and 158V alleles was related to a lower RR(p=0.018). The diplotypes containing 131H and 158V alleles had significantly lower RR than the other diplotypes(p=0.038).Our data suggest that FcgR polymorphisms may be associated with the outcome of mCRC patients treated with cetuximab and FOLFIRI. However, these results are currently controversial, and detailed investigations are needed to confirm the relationship between FcgRs polymorphisms and cetuximab efficacy.