免疫检查点抑制剂在晚期非小细胞肺癌中生存获益的性别差异：一项荟萃分析。
完整摘要 · 中文译文
背景：性别是否影响晚期非小细胞肺癌（NSCLC）中免疫检查点抑制剂（ICIs）的生存获益仍不确定。 方法：我们系统检索了PubMed、Embase、Cochrane Library、Web of Science和Scopus截至2026年4月1日的随机对照试验（RCTs），这些试验比较了ICIs与化疗，并按性别报告了总生存期（OS）或无进展生存期（PFS）。采用随机效应模型进行荟萃分析。 结果：共纳入63篇文献（报告42项3期RCTs），涉及25,827例患者（18,772例男性；7,055例女性）。与化疗相比，ICIs在男性和女性中均显著改善了OS和PFS（男性：OS：HR 0.74 [95% CI 0.71-0.78]；PFS：HR 0.59 [95% CI 0.54-0.64]；女性：OS：HR 0.83 [95% CI 0.77-0.90]；PFS：HR 0.76 [95% CI 0.66-0.86]）。汇总的治疗-by-性别交互作用分析显示，男性在OS（交互作用HR = 0.90 [95% CI 0.84-0.97]；P = 0.01）和PFS（交互作用HR = 0.82 [95% CI 0.73-0.92]；P = 0.0006）方面的获益显著大于女性。在亚组分析中，OS的性别差异在接受ICI单药治疗的患者中达到统计学显著性（P = 0.02），包括接受抗PD-1单药治疗的患者（P = 0.04）和PD-L1表达≥50%的患者（P = 0.02）。然而，这些差异在错误发现率（FDR）校正后未能持续存在（校正后P分别为0.07、0.10和0.07）。相比之下，PFS的性别差异在ICI单药治疗中经FDR校正后仍具有统计学显著性（校正后 P = 0.001）、抗PD-1单药治疗（校正P = 0.001）和PD-L1 ≥ 50%（校正P = 0.004）亚组。在接受ICI联合化疗的患者中，OS或PFS均未观察到显著的基于性别的差异。 结论：尽管ICI在两种性别中均优于化疗，但相对于男性，ICI单药治疗的PFS获益在女性中似乎有所减弱。鉴于基线混杂因素的不平衡以及纳入试验中女性代表性不足，这些发现应谨慎解读，并需要在未来专门设计用于研究性别差异的RCT中加以确认。
完整摘要 · 英文原文
BACKGROUND: Whether sex influences the survival benefit of immune checkpoint inhibitors (ICIs) in advanced non-small cell lung cancer (NSCLC) remains uncertain. METHODS: We systematically searched PubMed, Embase, Cochrane Library, Web of Science, and Scopus up to April 1, 2026, for randomized controlled trials (RCTs) comparing ICIs with chemotherapy and reporting overall survival (OS) or progression-free survival (PFS) stratified by sex. A random-effects model was used for meta-analysis. RESULTS: Sixty-three publications (reporting 42 phase 3 RCTs) involving 25,827 patients (18,772 male; 7,055 female) were included. Compared with chemotherapy, ICIs significantly improved both OS and PFS in males (OS: HR 0.74 [95% CI 0.71-0.78]; PFS: HR 0.59 [95% CI 0.54-0.64]) and females (OS: HR 0.83 [95% CI 0.77-0.90]; PFS: HR 0.76 [95% CI 0.66-0.86]). Pooled treatment-by-sex interaction analyses demonstrated significantly greater OS (interaction HR = 0.90 [95% CI 0.84-0.97]; P = 0.01) and PFS (interaction HR = 0.82 [95% CI 0.73-0.92]; P = 0.0006) benefits in males than in females. In subgroup analyses, sex‑based differences in OS reached statistical significance in patients receiving ICI monotherapy (P = 0.02), including those treated with anti‑PD‑1 monotherapy (P = 0.04) and those with PD‑L1 expression ≥50% (P = 0.02). However, these differences did not persist after the False Discovery Rate (FDR) correction (adjusted P = 0.07, 0.10, and 0.07, respectively). In contrast, sex‑based differences in PFS remained statistically significant after FDR correction in the ICI monotherapy (adjusted P = 0.001), anti‑PD‑1 monotherapy (adjusted P = 0.001), and PD‑L1 ≥ 50% (adjusted P = 0.004) subgroups. No significant sex‑based differences in either OS or PFS were observed among patients treated with ICI plus chemotherapy. CONCLUSIONS: Although ICIs are superior to chemotherapy in both sexes, the PFS benefit of ICI monotherapy appears to be attenuated in females relative to males. Given the imbalances in baseline confounders coupled with the underrepresentation of females in the included trials, these findings should be interpreted with caution and warrant confirmation in future RCTs designed specifically to investigate sex‑based differences.