【摘要】 目的 观察鼠类肉瘤病毒癌基因同源物B1(v-raf murine sarcoma viral oncogene homolog B1,BRAF)V600E突变、人表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)突变、转染重排(rearranged during transfection,RET)融合基因、表皮生长因子受体(epidermal growth factor receptor,EGFR) 20外显子插入(EGFR exon 20 insertion mutations,EGFR 20-ins)突变的晚期肺腺癌患者接受不同治疗方案的疗效和安全性，为指导临床提供依据。方法 采用回顾性队列研究设计方案，将2019年10月至2021年12月就诊于浙江大学附属第一医院的14例BRAF V600E突变患者、22例HER2突变患者、20例RET融合基因患者及15例EGFR 20-ins突变患者纳入本研究。将不同突变组患者分别分为化疗±贝伐珠单抗组、化疗+免疫检查点抑制剂(immune checkpoint inhibitors, ICIs)组及选择性靶向药组，比较各突变组内不同治疗方案的疗效和药物不良反应。结果 在BRAF V600E突变患者的一线治疗中，达拉非尼-曲美替尼组的中位无进展生存期(median progression-free survival, mPFS)优于化疗±贝伐珠单抗组及化疗+ICIs组，但差异无统计学意义(15.8 vs. 6.3 vs.4.7个月，P=0.426 5);在HER2阳性患者的一线治疗中，化疗+ICIs组的mPFS优于化疗±贝伐珠单抗组及HER2抑制剂组，差异有统计学意义(8.7 vs. 5.2 vs.2.9个月，P=0.013 5);在RET融合基因患者的一线治疗中，RET抑制剂组的mPFS优于化疗±贝伐珠单抗组及化疗+ICIs组，差异无统计学意义(17.5 vs. 7.8 vs. 6.7个月，P=0.092 3)。结论 选择性靶向药可能对BRAF V600E突变、RET融合基因晚期肺腺癌患者一线治疗更有效，而化疗联合免疫治疗可能对HER2阳性晚期肺腺癌患者一线治疗更有效。更多还原

【Abstract】 Objective To analyze the efficacy and safety of different treatments in advanced lung adenocarcinoma patients with v-raf murine sarcoma viral oncogene homolog B1(BRAF) V600E mutation, human epidermal growth factor receptor 2(HER2) mutation, rearranged during transfection(RET) fusion gene and EGFR exon 20 insertion(EGFR 20-ins)mutations in order to provide references for clinical guidance. Methods A retrospective cohort study was performed on 14 patients with BRAF V600E mutation, 22 patients with HER2 mutation, 20 patients with RET fusion gene and 15 patients with EGFR 20-ins mutation who were admitted to our hospital between October 2019 and December 2021. The patients from different mutation groups were divided into chemotherapy±bevacizumab subgroup, chemotherapy+immune checkpoint inhibitors(ICIs) subgroup, and selective targeted drug subgroup. The efficacy and adverse events were compared in each mutation group. Results In the first-line treatment of the patients with BRAF V600E mutation, the median progression-free survival(mPFS) was longer in the dabrafenib-trametinib subgroup than the chemotherapy±bevacizumab subgroup and chemotherapy+ICIs subgroup(15.8 vs 6.3 and 4.7 months, P=0.426 5), but there were significant differences. In the first-line treatment of HER2-positive patients, the mPFS in the chemotherapy+immune subgroup was statistically better than the chemotherapy±bevacizumab subgroup and the HER2 inhibitor subgroup(8.7 vs 5.2 and 2.9 months, P=0.013 5). In the first-line treatment of the patients with RET fusion gene, the mPFS in the RET inhibitor subgroup was longer than that of the chemotherapy±bevacizumab subgroup and that of the chemotherapy+ICIs subgroup, without statistical significances(17.5 vs 7.8 and 6.7 months, P=0.092 3). Conclusion Targeted therapeutic drugs may be more effective in advanced lung adenocarcinoma patients with BRAF V600E mutation and RET fusion gene than those at first-line, while chemotherapy combined with immunotherapy may be more effective in the patients with HER2-positive at first line.更多还原