Zhongguo Linchuang Yixue (Oct 2024)
Sex differences in the efficacy of first-line PD-1 blockade plus chemotherapy in patients with advanced lung adenocarcinoma
Abstract
ObjectiveTo 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. MethodsThe 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. ResultsIn 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. ConclusionsCompared 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.
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