Association between sex and outcomes in patients with non-small-cell lung cancer receiving combination chemoimmunotherapy as a first-line therapy: a systematic review and meta-analysis of randomized clinical trials

Introduction: Recently, several meta-analyses have investigated the association between sex and the efficacy of immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC). However, this issue remains controversial, because the results have been inconsistent. Moreover, the effect of sex on outcomes in patients with NSCLC receiving combination chemoimmunotherapy as a first-line therapy is poorly understood. The aim of this study was to examine the association between sex and outcomes in patients with NSCLC receiving combination chemoimmunotherapy as a first-line therapy.

Methods: We searched PubMed and Scopus from database inception to Feb 18, 2022 and performed a systematic review and meta-analysis of randomized and controlled clinical trials investigating ICI+non-ICI vs non-ICI as a first-line therapy in NSCLC. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS) in male and female patients were calculated using common and random-effects models.

Results: We analyzed 5,830 patients, comprising 4,137 (71.0%) males and 1,693 (29.0%) females, from nine randomized clinical trials. The pooled HR (95%CI) for OS comparing ICI+non-ICI vs non-ICI was 0.80 (0.72-0.87) for males and 0.69 (0.54-0.89) for females. The pooled HR (95%CI) for PFS comparing ICI+non-ICI vs non-ICI was 0.60 (0.55-0.66) for males and 0.56 (0.44-0.70) for females.

Conclusions: In patients with NSCLC receiving combination chemoimmunotherapy as a first-line therapy, a greater improvement in OS and PFS was observed in female patients than in male patients.