晚期胃癌一线免疫治疗有效性和安全性的网状分析

A network analysis of the safety and efficacy of first⁃line immunotherapy in treating advanced gastric cancer

目的:比较晚期胃癌一线免疫治疗的有效性和安全性。方法:通过查阅数据库,收集自2021年12月以来所有晚期胃癌一线免疫治疗的临床试验信息。使用总生存期、无进展生存期、客观缓解率和3~5级不良事件评价一线免疫治疗的有效性和安全性。使用程序性细胞死亡蛋白配体1(PD-L1)联合阳性分数(CPS)评分量化患者PD-L1的表达水平。结果:本研究共纳入3项Ⅲ期临床研究的3068名患者。相比化疗、帕博利珠单抗单药治疗、帕博利珠单抗联合化疗,纳武利尤单抗联合化疗在全人群中总生存期和无进展生存期较长。对于不同PD-L1 CPS评分患者进行不同一线免疫治疗,CPS≥5患者一线纳武利尤单抗联合化疗更能获益。对于不同PD-L1 CPS患者一线帕博利珠单抗单药治疗,相比化疗,只有CPS≥10患者有总生存获益。在安全性方面,相比化疗、帕博利珠单抗联合化疗、纳武利尤单抗联合化疗,帕博利珠单抗单药治疗发生≥3级不良事件较少。结论:不同PD-L1表达水平晚期胃癌患者接受一线免疫治疗的有效性和安全性存在显著差异。本研究结果有助于指导晚期胃癌患者的一线精准免疫治疗。

Objective:To compare the safety and efficacy of first⁃line immunotherapy in treating advanced gastric cancer.Methods:All clinical trials focused on first⁃line immunotherapy in advanced gastric can⁃cer were included in this study.The overall survival,progression⁃free survival,objective response rate,and Grade 3⁃5 adverse events were adopted to evaluate the efficacy and safety of immunothera⁃py.The advanced gastric patients were classified into subgroups based on the programmed cell death 1 ligand 1(PD⁃L1)Combined Positive Score(CPS).Results:A total of 3068 patients from 3 phaseⅢclinical trials were included in this study.Compared with chemotherapy,Pembrolizumab mono⁃therapy,Pembrolizumab combined chemotherapy,and Nivolumab combined chemotherapy had the most improvement in overall survival and progression⁃free survival.Among different PD⁃L1 CPS pa⁃tients treated by various first⁃line immunotherapies,PD⁃L1 CPS≥5 patients receiving Nivolumab combined chemotherapy had more benefits.In contrast to those who received chemotherapy,for different PD⁃L1 CPS patients receiving Pembrolizumab monotherapy,only CPS≥10 patients had pro⁃longed overall survival.Considering safety,compared with chemotherapy,Pembrolizumab combined chemotherapy,and Nivolumab combined chemotherapy,respectively,Pembrolizumab monotherapy had the fewest Grade 3⁃5 adverse events.Conclusion:The efficacy and safety of first⁃line immuno⁃therapy differed significantly in advanced gastric cancer patients with various PD⁃L1 expression levels.Our study could provide help in treating advanced gastric cancer with precision immunotherapy in clinic.