641P - FcγR IIA and IIIA polymorphisms predict clinical outcome of trastuzumab treated metastatic gastric cancer

Abstract

Trastuzumab has substantial anti-tumor activity in metastatic gastric cancer, and one mechanism is antibody-dependent cell-mediated cytotoxicity (ADCC), which has been reported to be influenced by FcγR II A and III A polymorphisms. This retrospective study is the first to assess their impact on trastuzumab efficacy in patients with metastatic gastric cancer. We retrospectively included 42 Her-2 positive patients receiving fluorouracil and platinum based chemotherapy and trastuzumab, and 68 Her-2 negative patients receiving fluorouracil and platinum based chemotherapy only as first line treatment. FcγR II A and III A polymorphisms were assessed and their associations with efficacy in both settings were analyzed. In patients treated with trastuzumab, FcγR II A H/H genotype was associated with significantly superior progression-free survival (PFS) (hazard ratio (HR) and 95% confidence interval (CI): 0.36 (0.16-0.82), adjusted HR and 95% CI: 0.18 (0.07-0.48), P = 0.001). Combining FcγR II A and III A polymorphisms, FcγR II A H/H or FcγRIII A V/V genotype was associated with significantly improved disease control rate (DCR) (P = 0.04) and PFS (HR and 95% CI: 0.29 (0.13-0.67), adjusted HR and 95% CI: 0.17 (0.07-0.45), P < 0.001). As expected, no association of FcγR II A and III A polymorphisms with efficacy was identified in patients receiving chemotherapy only. FcγR II A and III A polymorphisms might predict DCR and PFS in metastatic gastric cancer receiving trastuzumab treatment.