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

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSION: Compared to chemotherapy, immunotherapy can improve the prognosis of patients with advanced NSCLC. Meanwhile, there are sex differences in the efficacy of immunotherapy. KEY MESSAGE: 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.