晚期肺癌免疫检查点抑制剂治疗疗效影响因素分析

Analysis of factors influencing therapeutic effect of immune checkpoint inhibitor therapy for advanced lung cancer

目的分析晚期肺癌患者免疫检查点抑制剂治疗疗效,探索临床预测因素。方法回顾性分析2017年至2020年于浙江大学医学院附属杭州市肿瘤医院接受免疫检查点抑制剂治疗的84例晚期肺癌患者的临床资料,根据免疫治疗实体瘤反应评价标准(immune response evaluation criteria in solid tumor,iRECIST)进行最佳疗效评估,Kaplan-Meier法统计无进展生存期和总生存期。单因素和多因素Cox分险比例回归模型分析预后相关因素。结果84例晚期肺癌患者中,免疫完全缓解1例,免疫部分缓解25例,免疫疾病稳定34例,免疫疾病进展24例。中位总生存期为25.93个月,中位无进展生存期为6.90个月。多因素Cox回归分析显示,大剂量激素治疗史(HR=2.518,P=0.004)、二线及以上治疗(HR=2.394,P=0.003)和高中性粒细胞/淋巴细胞比值(neutrophil to lymphocyte ratio,NLR;HR=2.682,P=0.001)是晚期肺癌免疫治疗后无进展生存期的独立危险因素。大剂量激素治疗史(HR=3.216,P=0.002)和高NLR(HR=4.125,P<0.01)是总生存期的独立危险因素。结论免疫检查点抑制剂治疗是晚期肺癌一种有效的治疗方式。一线尽早使用免疫检查点抑制剂治疗能够增加生存获益,首次最佳疗效时NLR水平有一定的预后价值,使用大剂量激素与预后不佳有一定的相关性。

Objective To analyze the efficacy of immune checkpoint inhibitor therapy in patients with advanced lung cancer,and explore the prognosis factors.Methods Clinical data of 84 patients with advanced lung cancer who were treated with checkpoint inhibitor-based immunotherapy in Affiliated Hangzhou Cancer Hospital,Zhejiang University School of Medicine from 2017 to 2020 were retrospectively analyzed.Optimal efficacy was assessed according to immune response evaluation criteria in solid tumors(iRECIST),and progression-free survival(PFS)and overall survival(OS)were calculated by Kaplan-Meier survival analysis.Univariate and multivariate Cox-regression analyses were used to analyze prognostic factors.Results Among the 84 patients,only one patient had immune complete response,25 had immune partial response,34 had immune stable disease,and 24 had immune progressive disease.The median OS and PFS were 25.93 months and 6.90 months,respectively.Multivariate Cox regression analysis showed that application of highdose corticosteroids(HR=2.518,P=0.004),≥2 line therapy(HR=2.394,P=0.003),and higher neutrophil to lymphocyte ratio(NLR;HR=2.682,P=0.001)were independent risk factors for PFS.Application of high-dose corticosteroids(HR=3.216,P=0.002)and higher NLR(HR=4.125,P<0.01)were independent risk factors for OS.Conclusions Checkpoint inhibitor-based immunotherapy is an effective therapy for advanced lung cancer.Early use of first-line immunotherapy can increase the survival benefits,NLR level has a certain prognostic value at the first optimal efficacy,and the application of high-dose corticosteroids is associated with poor prognosis.