Immunotherapy in advanced gastroesophageal cancers: A meta‐analysis of sex‐based outcomes in overall survival

Immune-checkpoint-inhibition (ICI) represents the mainstay for treatment of advanced gastroesophageal cancer (GEC) in most cases. Sex differences in innate and adaptive immune responses are known to reflect distinct anti-tumor efficacy of ICI in female and male patients. However, most randomized controlled trials (RCTs) on ICI in GEC were conducted without taking sex differences into account. To address this uncertainty, we conducted a meta-analysis across first-line (1L) RCTs in advanced GEC. Systematic research was performed up to March 31, 2025. The primary endpoint was the pooled hazard ratio (HR) for overall survival (OS) in male and female patients, comparing ICI-based therapy versus control. The secondary objective was to assess the interaction between sex and treatment effect. A total of 15 RCTs were included (7 trials on ESCC and 8 trials on GEA). In male ESCC patients, the pooled HR for OS favored ICI with statistical significance (HR = 0.70, 95% CI = 0.65-0.76, P < .00001). In women, HR was 0.81 (95% CI = 0.61-1.07, P = .14). In GEA, ICI- based therapy showed significant survival benefits in both men (HR = 0.78, 95% CI = 0.73-0.83, P < .00001) and women (HR = 0.82, 95% CI = 0.75-0.90, P < .0001). The test for interaction between sexes and treatment effect indicated no significant difference in ICI efficacy between sexes in ESCC (Chi² = 1.02, P = .31) and GEA (Chi² = 0.78, P = .38). In advanced ESCC, only men showed a statistically significant OS benefit from ICI-based treatment, but the difference between sexes was not statistically significant. In GEA, both sexes had similar survival benefits.