Distributions of FcγRIIa-131 and FcγRIIIa-158 polymorphisms and clinical response to cetuximab in Japanese patients with metastatic colorectal cancer (mCRC).
565 Background: Polymorphisms in fragment C receptor (FcγR) are expected as a predictive biomarker of cetuximab (Cmab). Previous studies have convincingly confirmed the distributions (dists) of FcγR polymorphisms in Western population and shown the existence of linkage disequilibrium (LD) between FcγRIIa and FcγRIIIa polymorphisms. Meanwhile, the dists in Asian population have been unknown but a few studies for non-cancer patients have suggested the difference in dists between Asian and Western populations. We investigated the dists of FcγR polymorphisms and their association with clinical response to Cmab in Japanese mCRC patients. Methods: Ninety-three patients with irinotecan/oxaliplatin/5-FU-refractory mCRC and treated by Cmab plus irinotecan or Cmab monotherapy were retrospectively registered from 8 centers in Japan. FcγR polymorphisms were determined from genomic DNA extracted from peripheral blood samples based on the Multiplex allele-specific PCR method. Comparisons according to FcγR polymorphisms were evaluated using Fisher's exact test for response rate (RR) and log-rank test for progression-free survival curves (PFS). Results: The dists of FcγRIIa HH/HR/RR and FcγRIIIa VV/VF/FF were 68/30/2% and 4/40/56%, respectively (Table). The absence of LD between FcγRIIa and FcγRIIIa polymorphisms was confirmed (GENEPOP, p=0.526; Linkdis, p=0.146). Of 74 patients with KRAS wild-type and treated by Cmab plus irinotecan, no difference according to FcγR polymorphisms was observed in either RR (IIa: HH 37% vs. HR/RR 36%, p=1.00; IIIa: VV/VF 39% vs. FF 35%, p= 0.81) or PFS curves (IIa: HH vs. HR/RR, p=0.84; IIIa: VV/VF vs. FF, p=0.09). Similar results were seen in patients treated by cetuximab monotherapy. Conclusions: This study clarified an ethnic difference in the frequencies of FcγR polymorphisms. Associations between the polymorphisms and clinical response to Cmab did not reach a statistical significance. [Table: see text] No significant financial relationships to disclose.