Sex difference in response to non-small cell lung cancer immunotherapy: an updated meta-analysis

Studying sex differences in the efficacy of immunotherapy may contribute to the practice of the precision medicine, especially in non-small cell lung cancer (NSCLC), a kind of cancer with sexual bimorphism. Published randomized controlled trials (RCTs), published by PubMed, Medline, Embase, and Scopus, before 15 June 2022, testing immunotherapy (CTLA-4 or PD-1/L1 inhibitor alone, combination or with chemotherapy) versus non-immunotherapy (receiving chemotherapy or placebo only) were included to assess different efficacy between males and females. The primary endpoint was overall survival (OS). This meta-analysis was registered with PROSPERO (CRD42022298439). Sixteen RCTs, involving 10,155 patients with advanced NSCLC, was collected in this meta-analysis. The pooled HR comparing immunotherapy vs non-immunotherapy were 0.76 (95%CI 0.71–0.81) for males and 0.74 (95%CI 0.63–0.87) for females. The pooled HRs comparing immune-checkpoint inhibitors (ICIs) plus chemotherapy versus chemotherapy were 0.79 (95%CI 0.70–0.89) for males and 0.63 (95%CI 0.42–0.92) for females. The pooled HRs comparing ICIs versus chemotherapy were 0.74 (95%CI 0.67–0.81) for males and 0.83 (95%CI 0.73–0.95) for females. In squamous NSCLC, the pooled HRs comparing immunotherapy vs non-immunotherapy were 0.73 (95%CI 0.58–0.91) for males and 0.74 (95%CI 0.37–1.48) for females. In non-squamous NSCLC, the pooled HRs comparing immunotherapy versus non-immunotherapy were 0.62 (95%CI 0.71–0.94) for males and 0.59 (95%CI 0.39–0.89) for females. Compared to chemotherapy, immunotherapy can improve the prognosis of patients with advanced NSCLC. Meanwhile, there are sex differences in the efficacy of immunotherapy.KEY MESSAGECompared to chemotherapy, immunotherapy can improve the prognosis of patients with advanced NSCLC.The most interesting thing in this study is that immunotherapy showed significant sex differences in the treatment of squamous NSCLC. Compared to chemotherapy, immunotherapy can improve the prognosis of patients with advanced NSCLC. The most interesting thing in this study is that immunotherapy showed significant sex differences in the treatment of squamous NSCLC.

探究免疫治疗疗效的性别差异，有助于推动精准医学的临床实践，在存在性别二态性的非小细胞肺癌（non-small cell lung cancer, NSCLC）中尤为关键。本研究纳入2022年6月15日前发表于PubMed、Medline、Embase及Scopus数据库的随机对照试验（randomized controlled trials, RCTs），这些试验对比了免疫治疗（单用CTLA-4或PD-1/L1抑制剂、联合治疗或联合化疗）与非免疫治疗（仅接受化疗或安慰剂）的疗效，旨在评估男性与女性患者的疗效差异。本研究的主要终点为总生存期（overall survival, OS）。本次荟萃分析已在PROSPERO平台注册（CRD42022298439）。本荟萃分析共纳入16项随机对照试验，涉及10155例晚期非小细胞肺癌患者。免疫治疗对比非免疫治疗的合并风险比（hazard ratio, HR）：男性为0.76（95%置信区间0.71–0.81），女性为0.74（95%置信区间0.63–0.87）。免疫检查点抑制剂（immune-checkpoint inhibitors, ICIs）联合化疗对比单纯化疗的合并HR：男性为0.79（95%置信区间0.70–0.89），女性为0.63（95%置信区间0.42–0.92）。免疫检查点抑制剂对比单纯化疗的合并HR：男性为0.74（95%置信区间0.67–0.81），女性为0.83（95%置信区间0.73–0.95）。在鳞状非小细胞肺癌患者中，免疫治疗对比非免疫治疗的合并HR：男性为0.73（95%置信区间0.58–0.91），女性为0.74（95%置信区间0.37–1.48）。在非鳞状非小细胞肺癌患者中，免疫治疗对比非免疫治疗的合并HR：男性为0.62（95%置信区间0.71–0.94），女性为0.59（95%置信区间0.39–0.89）。与单纯化疗相比，免疫治疗可改善晚期非小细胞肺癌患者的预后。同时，免疫治疗的疗效存在性别差异。核心要点：与单纯化疗相比，免疫治疗可改善晚期非小细胞肺癌患者的预后。本研究最引人关注的发现为，免疫治疗在鳞状非小细胞肺癌的治疗中存在显著的性别差异。与单纯化疗相比，免疫治疗可改善晚期非小细胞肺癌患者的预后。本研究最引人关注的发现为，免疫治疗在鳞状非小细胞肺癌的治疗中存在显著的性别差异。