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 FcɣR 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. FcɣR II A and III A polymorphisms were assessed and their associations with efficacy in both settings were analyzed.
In patients treated with trastuzumab, FcɣR 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 FcɣR II A and III A polymorphisms, FcɣR II A H/H or FcɣRIII 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
FcɣR II A and III A polymorphisms might predict DCR and PFS in metastatic gastric cancer receiving trastuzumab treatment.
Clinical trial identification
Legal entity responsible for the study
Major Special Project from Guangzhou Health and Medical Collaborative Innovation (No. 201508020247).
All authors have declared no conflicts of interest.