Sex-based survival differences in patients with untreated advanced oesophageal squamous cell carcinoma receiving chemotherapy and immune checkpoint inhibitors: a meta-analysis

Abstract

Purpose Chemotherapy combined with immune checkpoint inhibitors (ICIs) is the standard first-line treatment for patients with advanced oesophageal squamous cell carcinoma (OSCC). Evidence from other tumour types suggests that biological sex may influence ICI efficacy, but this remains unclear in OSCC. Patients and methods We conducted a systematic review and meta-analysis of phase III randomised trials comparing chemotherapy plus ICIs with chemotherapy alone in advanced OSCC. Overall survival (OS) was the primary endpoint, stratified by sex. Results Eight trials comprising 4904 patients (14.7% female) were analysed. Chemotherapy plus ICIs significantly improved OS overall [hazard ratio (HR) 0.68, 95% confidence interval (CI) 0.62-0.73], in females (HR 0.79, 95% CI 0.64-0.98, I² = 19%), and in males (HR 0.68, 95% CI 0.63-0.74, I² = 0%). Subgroup testing ( P = 0.19, I² = 42.8%) indicated moderate heterogeneity; however, meta-regression analysis ( P = 0.20) showed no significant interaction by sex. Sensitivity analysis revealed that the survival benefit in females was mainly driven by two studies. Conclusions Chemotherapy plus ICIs improves OS in both sexes, although the magnitude is less in females. These findings highlight the importance of considering sex as a biological variable in the design and interpretation of future clinical trials.