S1013 Platinum-Based Chemo + Anti-PD-1 Cuts Death Risk by One-Third in Esophageal Squamous Cell Carcinoma—A Sex-Disaggregated Meta-Analysis of Five Randomized Controlled Trials

Introduction: Immune-checkpoint blockade combined with platinum-based chemotherapy has transformed first-line care for advanced esophageal squamous-cell carcinoma (ESCC), yet the extent to which biological sex modulates this survival gain is uncertain. Females remain underrepresented in pivotal immunotherapy trials, raising concern that efficacy signals may be driven by male-predominant cohorts. To address this knowledge gap, we conducted a subgroup-level meta-analysis to quantify sex-specific overall-survival (OS) benefit with chemo-immunotherapy. Methods: A systematic literature search of PubMed, Embase, Scopus, and Cochrane Library databases was done to collect randomized controlled trials (RCTs) comparing platinum-based chemotherapy with anti-PD-1 antibody versus chemotherapy alone for overall survival (OS) in esophageal cancer, stratified by sex. Statistics was done by R (v4.4.3), with the restricted maximum likelihood estimator for between-study variance and Hartung-Knapp adjustment with random-effects/common effects model. Hazard ratios (HRs) and 95% confidence intervals (CIs) for male and female subgroups were extracted and log HRs and standard errors were derived from reported CIs. Sex subgroup analysis and interaction testing were conducted and Heterogeneity assessed using the I² statistic. Results: Across 5 first-line phase-III RCTs, the addition of a programmed cell death protein 1 (PD-1) inhibitor to standard chemotherapy significantly improved overall survival compared with chemotherapy alone (random-effects HR 0.64; 95% CI 0.55-0.74; I² = 38%). The survival advantage was evident in both men (HR 0.63; 95% CI 0.52-0.75; I² = 37%) and women (HR 0.67; 95% CI 0.38-1.19; I² = 49%), with no statistically significant interaction between sex and treatment effect (test for subgroup differences P = 0.73). A pooled ratio-of-hazard-ratios (female/male) of 1.07 (95% CI 0.56-2.08; I² = 52%) confirmed that the magnitude of benefit was comparable across. Conclusion: Chemo-immunotherapy slashes first-line ESCC mortality by ∼36% versus chemotherapy alone; the gain is near-identical in men (HR 0.63) and women (HR 0.67), with no sex-treatment interaction (P = 0.73). Our results show sex should no longer sway regimen choice—every eligible patient deserves PD-1 plus platinum-fluoropyrimidine. While moderate heterogeneity and wide female CIs reflect <20% female enrollment, the uniformly favorable direction across 5 global RCTs supports an immediate guideline upgrade and demands future trials recruit women equitably and report sex-specific outcomes.