Gender Differences and Their Effects on Survival Outcomes in Lung Cancer Patients Treated With PD-1/PD-L1 Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.

Aims: Programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) immune checkpoint inhibitors have had a major impact on the approach to care of patients with lung cancer. An important issue that is not known is whether they benefit men and women the same. We conducted a meta-analysis of all randomised controlled trials evaluating PD-1/PD-L1 inhibition in patients with non-small cell lung cancer (NSCLC) to determine if clinical response and survival are influenced by gender.

Materials And Methods: A PubMed search was carried out to identify all randomised controlled trials evaluating PD-1/PD-L1 inhibitors compared with conventional chemotherapy in NSCLC. Random-effects meta-analysis and meta-regression were performed to assess overall survival and progression-free survival (PFS) and whether there were differences in these outcomes between men and women.

Results: In total, 12 studies with data for overall survival and 11 studies with data for PFS were included. Immunotherapy showed a statistically significant benefit over chemotherapy for overall survival (pooled hazard ratio = 0.72, 95% confidence interval = 0.65-0.81, P < 0.001) and progression-free survival (pooled hazard ratio = 0.62, 95% confidence interval = 0.54-0.72, P < 0.001). We did not find a statistically significant difference between men and women in terms of overall survival (males versus females: pooled hazard ratio = 0.74, 95% confidence interval = 0.66-0.83 versus pooled hazard ratio = 0.72, 95% confidence interval = 0.63-0.82, P = 0.709) or progression-free survival (males versus females: pooled hazard ratio = 0.63, 95% confidence interval = 0.53-0.75 versus pooled hazard ratio = 0.72, 95% confidence interval = 0.58-0.88, P = 0.372).

Conclusion: This is the first systematic review and meta-analysis investigating the effect of gender and response to PD-1/PD-L1 checkpoint inhibitors in patients solely with NSCLC. We examined 9270 and 6193 patients in terms of overall survival and PFS, respectively. Although there are significant biological differences between men's and women's immune responses, we have shown that these drugs offer the same survival benefit in patients with NSCLC regardless of gender.