FcγRIIA and IIIA polymorphisms predict clinical outcome of trastuzumab-treated metastatic gastric cancer.
FcγRIIA and IIIA polymorphisms predict clinical outcome of trastuzumab-treated metastatic gastric cancer.
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Fc gamma RIIA 和 IIIA 多态性预测曲妥珠单抗治疗的转移性胃癌的临床结果
DOI：
10.2147/ott.s142620
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发表时间：
2017
影响因子：
4
通讯作者：
Xu RH
中科院分区：
文献类型：
--
作者：
Wang DS;Wei XL;Wang ZQ;Lu YX;Shi SM;Wang N;Qiu MZ;Wang FH;Wang RJ;Li YH;Xu RH
曲妥珠单抗在转移性胃癌中具有显著的抗肿瘤活性。其发挥抗肿瘤活性的机制之一是抗体依赖性细胞介导的细胞毒性，据报道其受到FcγRIIA和IIIA多态性的影响。这项研究是第一个评估其对转移性胃癌患者曲妥珠单抗疗效的影响。我们回顾性研究了42例接受氟尿嘧啶和铂类为基础的化疗和曲妥珠单抗的Her-2阳性患者，以及68例仅接受氟尿嘧啶和铂类为基础的化疗作为一线治疗的Her-2阴性患者。评估FcγRIIA和IIIA多态性，并分析其与两种情况下疗效的相关性。在接受曲妥珠单抗治疗的患者中，FcγRIIA H/H基因型与显著的上级无进展生存期（PFS）相关（风险比[HR] [95% CI]：0.36 [0.16-0.82]，校正HR [95% CI]：0.18 [0.07-0.48]，P=0.001）。当结合FcγRIIA和IIIA多态性时，FcγRIIA H/H或FcγRIIIA V/V基因型与疾病控制率（P=0.04）和PFS显著改善相关（HR [95% CI]：0.29 [0.13-0.67]，校正HR [95% CI]：0.17 [0.07-0.45]，P<0.001）。正如预期的那样，在仅接受化疗的患者中未发现FcγRIIA和IIIA多态性与疗效相关。我们得出结论，FcγRIIA和IIIA多态性可能预测接受曲妥珠单抗治疗的转移性胃癌患者的疾病控制率和PFS。
Trastuzumab has substantial antitumor activity in metastatic gastric cancer. One such mechanism by which it exerts its antitumor activity is antibody-dependent cell-mediated cytotoxicity, which has been reported to be influenced by FcγRIIA and IIIA polymorphisms. This study is the first to assess their impact on trastuzumab efficacy in patients with metastatic gastric cancer. We retrospectively examined 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 the first-line treatment. FcγRIIA and IIIA polymorphisms were assessed, and their associations with efficacy in both settings were analyzed. In patients treated with trastuzumab, the FcγRIIA H/H genotype was associated with significantly superior progression-free survival (PFS) (hazard ratio [HR] [95% CI]: 0.36 [0.16–0.82], adjusted HR [95% CI]: 0.18 [0.07–0.48], P=0.001). When combining FcγRIIA and IIIA polymorphisms, the FcγRIIA H/H or FcγRIIIA V/V genotype was associated with a significantly improved disease control rate (P=0.04) and PFS (HR [95% CI]: 0.29 [0.13–0.67], adjusted HR [95% CI]: 0.17 [0.07–0.45], P<0.001). As expected, no association of FcγRIIA and IIIA polymorphisms with efficacy was found in patients receiving chemotherapy only. We concluded that FcγRIIA and IIIA polymorphisms might predict disease control rate and PFS in metastatic gastric cancer patients receiving trastuzumab treatment.