Sex difference in survival benefits of immune checkpoint inhibitors in advanced non-small cell lung cancer: A 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.