FcγR and EGFR polymorphisms as predictive markers of cetuximab efficacy in metastatic colorectal cancer.

Abstract

Cetuximab shows activity in KRAS (Kirsten rat sarcoma viral oncogene homolog) wild-type metastatic colorectal cancer (mCRC). Recent studies have demonstrated that cetuximab induces antibody-dependent cell-mediated cytotoxicity (ADCC) in mCRC. We investigated the associations of FcγR (fragmentC γreceptor) and EGFR (epidermal growth factor receptor) polymorphisms with the outcome of mCRC patients treated with cetuximab and FOLFIRI (folic acid/5-fluorouracil/irinotecan) as second-line therapy in the FLIER (Cetuximab Plus Folinic Acid/5-Fluorouracil/Irinotecan in KRAS Wild-Type Metastatic Colorectal Cancer as a Second-Line Treatment) study. A total of 57 patients were evaluated in this study. The association of each polymorphism with the response rate, progression-free survival, and overall survival was analyzed. A tendency for longer overall survival was observed in patients with the EGFR CA repeat ≥36 genotype than in those with the ≤35 genotype (600 versus 483days, P=0.051). The haplotype containing the 131H and 158V alleles was associated with a lower response rate than the other haplotypes (P=0.018). These results are contrary to previously published results. Our data suggest that FcγR and EGFR CA repeat polymorphisms may be associated with the outcome of mCRC patients treated with cetuximab and FOLFIRI, although further investigations will be needed to confirm the association of FcγR and EGFR polymorphisms with the efficacy of cetuximab.