Sex-related differences in the efficacy of immune checkpoint inhibitors in malignancy: a systematic review and meta-analysis

Although disease susceptibility is known to differ between men and women, it is controversial whether the efficacy of immune checkpoint inhibitors for malignancies also differs between the sexes. We conducted a meta-analysis to explore the impact of sex on immune checkpoint inhibitor treatment outcomes. We searched PubMed, Embase and the Cochrane Library databases from inception to October 1, 2020 for randomized controlled trials of immune checkpoint inhibitors with hazard ratios (HRs) stratified by sex. We calculated the pooled HRs for men and women using the ln(HR), and assessed the heterogeneity between the two estimates through an interaction test. In total, 22,268 patients from 39 randomized controlled trials were included. Immune checkpoint inhibitors yielded better overall survival than conventional agents in both men (HR: 0.75, 95% confidence interval [CI]: 0.71–0.80) and women (HR: 0.77, 95% CI: 0.70–0.85). Progression-free survival benefits were also observed in both men (HR: 0.64, 95% CI: 0.58–0.70) and women (HR: 0.67, 95% CI: 0.58–0.77) treated with immune checkpoint inhibitors. No sex differences in the response to immune checkpoint inhibitors were found when overall survival and progression-free survival were used as the endpoints.