Effect of sex on the efficacy of patients receiving immune checkpoint inhibitors in advanced non-small cell lung cancer

Immune checkpoint inhibitors (ICIs) have shown promising efficacy in the treatment of non-small cell lung cancer (NSCLC). Sex-associated dimorphism in immune system response is acknowledged, but the effect of patients' sex on efficacy of ICIs as treatment in NSCLC still remains controversial. The present study was conducted to investigate the difference in efficacy of NSCLC patients receiving immune checkpoint inhibitors according to the sex. A total of 9583 patients involved 6567 men and 3016 women with advanced lung cancer from 15 randomized controlled trials were included in this study. An overall survival (OS) benefit of immune checkpoint inhibitors was illustrated in both male (HR 0.76, 95% CI 0.71-0.82) and female (HR 0.73, 95% CI 0.58-0.91) patients, and a progression-free survival (PFS) benefit was also found in both men (HR 0.67, 95% CI 0.58-0.77) and women (HR 0.73, 95% CI 0.56-0.95) in NSCLC. Both PD-1/PD-L1 inhibitors alone and PD-1/PD-L1 plus chemotherapy significantly improved the OS and PFS in male patients. Whereas in females, PD-1 inhibitors or monotherapy significantly benefited the OS but not the PFS, PD-L1 inhibitors or combination therapy significantly prolonged the PFS but not the OS. No survival benefit was found in both male and female patients from the CTLA-4 inhibitors. The current study indicated that the magnitude of survival benefit is sex-dependent and male patients seemed to obtain more consistent and favorable outcomes from ICIs than women patients in NSCLC.