中国临床医学2024，Vol.31Issue(5)：757-764,8.DOI:10.12025/j.issn.1008-6358.2024.20240583
晚期肺腺癌患者接受一线程序性死亡受体1抗体联合化疗疗效的性别差异
Sex differences in the efficacy of first-line PD-1 blockade plus chemotherapy in patients with advanced lung adenocarcinoma
摘要
Abstract
Objective To explore the impact of sex on the efficacy of first-line programmed death-1(PD-1)blockade plus chemotherapy in patients with advanced lung adenocarcinoma and its potential biological mechanisms.Methods The clinical and pathological characteristics and follow-up data of 163 patients with advanced lung adenocarcinoma without driver gene alterations at Shanghai Pulmonary Hospital affiliated to Tongji University from October 2018 to October 2023 were retrospectively collected.Among them,103 patients received first-line PD-1 blockade plus chemotherapy(51 males and 52 females)and 60 patients received first-line standard platinum-based doublet chemotherapy(39 males and 21 females).Patients were divided into male group and female group.Clinical characteristics,efficacy,progression-free survival(PFS),and overall survival(OS)were compared between the two groups.Kaplan-Meier method was used to plot the survival curves of male and female patients,and log-rank test was used for significance evaluation.Cox proportional hazards model was used to analyze the factors influencing PFS and OS.Multiplex immunofluorescence(mIF)assays were used to analyze the differences of protein expression levels of programmed death-ligand 1(PD-L1),CD8,CD68,CD4,and FOXP3 between male and female groups in baseline tumor sample.Results In patients receiving first-line PD-1 blockade plus chemotherapy,the median PFS in female group and male group was 13.0 months and 6.8 months,respectively(HR=0.39,95% CI 0.25-0.62;P＜0.01).The median OS in female group and male group was 46.2 months and 17.3 months,respectively(HR=0.30,95% CI 0.18-0.50;P＜0.01).In patients receiving first-line chemotherapy,the median PFS in female group and male group was 5.7 months and 5.5 months,respectively(P＞0.05);the median OS in female group and male group was 21.7 months and 17.7 months,respectively(P＞0.05).The results of the Cox proportional hazards model showed that sex was an independent factor influencing PFS and OS in patients receiving first-line PD-1 blockade plus chemotherapy(P＜0.05).The results of mIF showed that pretreatment tumor samples of female patients had a significantly higher expression level of CD8 than male patients(P＜0.05),while the expression level of PD-L1,CD68,CD4 and FOXP3 was similar between female and male groups.Conclusions Compared to male patients,female patients with advanced lung adenocarcinoma benefit more from the first-line PD-1 blockade plus chemotherapy.The increased expression level of CD8 in pretreatment tumor samples of female patients would be the potential mechanism.关键词
肺腺癌/程序性死亡受体1抗体/化疗/性别Key words
lung adenocarcinoma/programmed death-1 blockade/chemotherapy/sex分类
医药卫生引用本文复制引用
申辉,张洪涛,王浩伟,蒋涛,赵凤德..晚期肺腺癌患者接受一线程序性死亡受体1抗体联合化疗疗效的性别差异[J].中国临床医学,2024,31(5):757-764,8.基金项目
上海市 2023 年度"科技创新行动计划"医学创新专项项目(23Y11904100).Supported by Shanghai 2023"Science and Technology Innovation Action Plan"Medical Innovation Special Project(23Y11904100). （23Y11904100）
