Meta-analysis finds sex-based differences in ICI survival benefit for advanced gastroesophageal cancer

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International journal of cancer Published May 15, 2026 Medically reviewed May 15, 2026 Study authors: Masetti Michael, Petrelli Fausto, Pietrantonio Filippo, Lorenzen Sylvie, Leone Alberto Giovanni PubMed ↗ DOI ↗ By Dr. Lars van Dijk, PhD · Surgical, Procedural & Diagnostic

Key Takeaway

Consider that this meta-analysis reports a significant OS benefit for ICI in men but not women with esophageal squamous cell carcinoma.

This is a meta-analysis of 15 randomized controlled trials evaluating immune-checkpoint inhibition (ICI) for advanced gastroesophageal cancer. The primary outcome was the pooled hazard ratio for overall survival. The analysis found a significant survival benefit for ICI over control in male patients with esophageal squamous cell carcinoma (HR = 0.70, 95% CI = 0.65-0.76, P < .00001). In female patients with this cancer, the benefit was not statistically significant (HR = 0.81, 95% CI = 0.61-1.07, P = .14).

For patients with gastric or gastroesophageal junction cancer, the meta-analysis found a significant survival benefit for ICI 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 analysis of interaction between sex and treatment effect found no significant difference in ICI efficacy between sexes for either esophageal squamous cell carcinoma (Chi = 1.02, P = .31) or gastric/gastroesophageal junction cancer (Chi = 0.78, P = .38).

A key limitation noted by the authors is that most randomized controlled trials on ICI in gastroesophageal cancer were conducted without taking sex differences into account. Safety data were not reported in the source abstract. The practice relevance was not reported. The findings suggest a potential sex-based difference in treatment effect for esophageal squamous cell carcinoma, but this should be interpreted with caution given the limitations.

Study Details

Study typeMeta analysis

EvidenceLevel 1

PublishedMay 2026

PMID41439471

View Original Abstract ↓

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 (Chi = 1.02, P = .31) and GEA (Chi = 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.