EGFR突变晚期非小细胞肺癌患者后线接受免疫治疗的疗效分析  

Analysis of the Efficacy of Immunotherapy on the Posterior Lines of Advanced EGFR Mutant Patients with Non-small Cell Lung Cancer

作　　者：马丽[1] 秦娜[1] 张新勇[1] 吴羽华[1] 李浩洋 俞孟军 刘子臣[2] 王敬慧[3] Ma Li;Qin Na;Zhang Xinyong;Wu Yuhua;Li Haoyang;Yu Mengjun;Liu Ziehen;Wang Jinghui(Department of Medical Oncology,Beijing Chest Hospital,Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute,Beijing 101149,China;不详)

机构地区：[1]首都医科大学附属北京胸科医院/北京市结核病胸部肿瘤研究所肿瘤内科,北京101149 [2]首都医科大学附属北京胸科医院/北京市结核病胸部肿瘤研究所病理科,北京101149 [3]首都医科大学附属北京胸科医院/北京市结核病胸部肿瘤研究所肿瘤研究中心,北京101149

出　　处：《结核病与胸部肿瘤》2021年第3期195-200,共6页Tuberculosis and Thoracic Tumor

基　　金：首都卫生发展科研专项基金-青年优才项目(No.2018-4-1043);北京市医管中心青苗计划(No.QML20181602)资助。

摘　　要：背景与目的免疫检查点抑制剂单药治疗在驱动基因阳性的晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者中疗效甚微。研究表明,部分驱动基因阳性患者靶向治疗耐药后对免疫联合治疗仍有效。国内研究甚少。本研究旨在分析人表皮生长因子(epidermal growth factor receptor,EGFR)敏感突变NSCLC患者后线接受免疫治疗的疗效,评价真实世界免疫联合化疗在突变晚期患者后线治疗中的价值。方法收集2018年6月-2020年11月在首都医科大学附属北京胸科医院确诊的fGF/T突变的初治晚期肺腺癌患者共27例,均在靶向治疗进展后接受了程序性死亡受体1(programmed cell death protein 1,PD-1)检查点抑制剂联合化疗以及抗血管生成药物治疗。结果27例晚期NSCLC患者中,未合并T790M突变的有19例(70.4%),合并T790M点突变的有8例(29.6%)。总客观缓解率为40.7%。Kaplan-Meier生存分析显示,不同突变类型之间接受含PD-1单抗治疗的无进展生存期(progression-free survival,PFS)均无统计学差异(χ^(2)=4.15,P=0.23)。未合并T790M突变的患者PFS较合并T790M突变的患者显著延长(9.2个月vs3.3个月,χ^(2)=2.81,P=0.041),两者总生存时间未见统计学差异(12.2个月vs7.3个月,χ^(2)=3.22,P=0.062)。未合并T790M的客观缓解率明显优于合并T790M的患者(52.63%vs 12.5%,P=0.045)。结论突变患者人群能从后线免疫联合治疗中获益,但合并T790M突变的患者后线接受免疫联合治疗疗效差。因此,这部分患者的后续治疗和全程化管理需要探索更优的治疗策略来提高获益。Background and objective Immune checkpoint inhibitor monotherapy is reported to have litle effect in advanced non-small cell lung cancer(NSCLC)patients with driver oncogenes.However,recent studies have shown that some patients with driver genes are still benefit from combination immunotherapy afer tyrosine kinase inhibitors(TKIs)drug resistance.The purpose of this study was to analyze the efficacy of posterior line immunotherapy in NSCLC patients with epidermal growth factor(EGFR)sensitive mutation,and to evaluate the value of immunotherapy in posterior line therapy in patients with advanced EGFR mutation.Methods A total of 27 patients with EGFR mutation diagnosed in Beijing Chest Hospital,Capital Medical University from June 2018 to November 2020 were collected.Afer the progress of targeted therapy,they had received programmed cell death protein 1(PD-1)checkpoint inhibitor combined with chemotherapy and anti-angiogenic drug therapy.Results Of the 27 advanced NSCLC patients,19 cases(70.4%)did not have T790M mutation.There were 8 cases(29.6%)with T790M point mutation.The total objective response rate(ORR)was 40.7%.Kaplan-Meier survival analysis showed that there was no statistically significant difference among different EGFR mutations(χ^(2)=4.15,P=0.230).But progression-free survival(PFS)was significantly longer in patients without T790M mutation than in patients with T790M mutation(9.2 mon vs 3.3 mon,χ^(2)=2.808,P=0.041),and the same trend was observed in patients with overall survival treated with the PD-1 inhibitor(12.2 mon vs 7.3 mon,χ^(2)=3.22,P=0.062).ORR of patients without T790M was significantly beter than that with T790M(52.63%vs 12.5%,P=0.045).Conclusion Patients with EGFR mutation can benefit from later-line combined immunotherapy.The patients with T790M mutation in the population of EGFR mutation had the worst effect of immunotherapy in the later line.Therefore,the follow-up treatment and whole-course management of these patients need to explore better treatment strategies to improve the benefit.

关 键 词：肺肿瘤 表皮生长因子受体 基因突变 免疫治疗 

分 类 号：R73[医药卫生—肿瘤]