包含罕见突变的EGFR双突变非小细胞肺癌患者的TKI疗效分析

Analysis of effectiveness of tyrosine kinase inhibitors in non-small cell lung cancer patients with epidermal growth factor receptor double mutations containing rare mutations

目的探索包含罕见突变的表皮生长因子受体（EGFR）双突变非小细胞肺癌（NSCLC）患者的EGFR酪氨酸激酶抑制剂（EGFRTKI）的疗效。方法收集2007年3月至2017年1月，武汉大学人民医院、武汉大学中南医院和湖北省肿瘤医院经组织病理学和EGFR基因检测证实的包含罕见突变的EGFR双突变患者。根据突变类型，患者分为EGFR敏感突变复合敏感突变组和敏感突变复合耐药突变组。分析包含罕见突变的EGFR双突变患者及不同突变类型患者接受EGFRTKI的疗效。结果2 637例NSCLC患者接受EGFR突变检测，其中包含罕见突变的EGFR双突变患者19例。15例接受EGFRTKI治疗，客观缓解率（ORR）为46.7%（7/15），疾病控制率（DCR）为73.3%（11/15），中位无进展生存期（PFS）为8.1个月。敏感突变复合敏感突变组部分缓解2例，疾病稳定1例。敏感突变复合耐药突变组部分缓解5例，疾病稳定3例，无效4例。结论包含罕见突变的EGFR双突变患者接受EGFRTKI疗效尚可，可为该类患者的临床治疗提供参考。

ObjectiveTo explore the effectiveness of epidermal growth factor receptor （EGFR）tyrosine kinase inhibitors （TKIs） in nonsmall cell lung cancer （NSCLC） patients with EGFR double mutations containing rare mutations. MethodsFrom March 2007 to January 2017, NSCLC patients with EGFR double mutations containing rare mutations confirmed by histopathology and EGFR mutation detections at Renmin Hospital of Wuhan University, Zhongnan Hospital of Wuhan University and Hubei Cancer Hospital were enrolled. According to the mutation types, patients were divided into double activating mutations group and activating mutations with insensitive mutations group. The effectiveness of TKIs in NSCLC patients with EGFR double mutations containing rare mutations and different mutation types was analysis. ResultsAmong the 2 637 NSCLC patients underwent EGFR mutation detections, 19 patients were confirmed as EGFR double mutations containing rare mutations. Fifteen patients received EGFRTKIs therapy, the objective response rate （ORR）, disease control rate （DCR） and median progression free survival （PFS） were 46.7% （7/15）, 73.3% （11/15） and 8.1 months, respectively. In patients with double activating mutations, two patients had partial response （PR）, one patient had a stable disease （SD）. In the activating mutations with insensitive mutations group, five patients had PR, three patients had SD, four patients had no effect. ConclusionPatients with EGFR double mutations containing rare mutations have a general response to EGFRTKIs, and this result can provide a reference for the treatment of those patients.