Sex-based responses to immunotherapy in esophageal cancer: insights from a meta-analysis

Sex-based disparities in immune-related adverse events and immune response remain to be fully elucidated. In this study, we aim to explore the efficacy of immunotherapy in esophageal cancer (EC) in response to patient sex. The study followed the guidelines of Preferred Reporting Items for the Systematic review and Meta-Analyses (PRISMA). PubMed, EMBASE, Web of Science, Scopus, and the Cochrane Library were searched to compare immunotherapy outcomes in male and female EC patients from clinical trials. The ratio of hazard ratios (HRs) and 95% CI between males and females from each individual study was calculated and then pooled to provide a weighted average. A meta-analysis was performed using R software. Fifteen randomized clinical trials involving 7430 male (80.47%) and 1803 female (19.53%) EC patients were included. PD-1 inhibitors were most predominant immunotherapeutic interventions. Compared to control groups, patients receiving immunotherapy showed significantly lower HRs for OS and PFS in both male (OS: HR = 0.73, 95% CI 0.69–0.78; PFS: HR = 0.56, 95% CI 0.51–0.63) and female patients (OS: HR = 0.76, 95% CI 0.67–0.87; PFS: HR = 0.63, 95% CI 0.54–0.74). Subgroup analyses revealed no significant differences in immunotherapy efficacy between two sexes. Immunotherapy is a beneficial treatment option for EC patients of both sexes, but no significant sex-based differences in immunotherapy efficacy were observed in the current study. Future studies are warranted to investigate the efficacy disparity of different immunotherapeutic drugs in male and female patients.