Do Men and Women Respond Differently to Immunotherapy in Advanced Oesophagal Squamous Cell Carcinoma: ESMO Gastrointestinal Oncology | August 2026

Introduction:

The combination of chemotherapy and immune checkpoint inhibitors (ICIs) is now the standard first-line treatment for advanced oesophagal squamous cell carcinoma (ESCC). Emerging evidence from several cancers suggests that biological sex may influence immunotherapy response, but whether this affects outcomes in ESCC has remained uncertain. This meta-analysis evaluated whether survival benefits from chemo-immunotherapy differ between men and women.

Why was this study needed?

Chemotherapy plus ICIs has become the standard first-line treatment for advanced ESCC.

Biological sex is increasingly recognized as an important determinant of immune response.

Previous individual trials have reported inconsistent findings regarding sex-specific benefit.

Understanding sex-related differences may improve trial design and personalized treatment strategies.

Robust pooled evidence was lacking.

Results:

This meta-analysis included 8 Phase III randomized trials involving 4,904 patients with untreated advanced ESCC.

Chemotherapy plus immunotherapy significantly improved overall survival in both men and women compared with chemotherapy alone.

The survival benefit was numerically greater in men than in women.

Although women still derived meaningful benefit from immunotherapy, the magnitude of improvement appeared smaller.

Importantly, statistical analyses did not demonstrate a significant interaction between sex and treatment effect, indicating that current evidence is insufficient to conclude that biological sex independently predicts immunotherapy benefit.

Sensitivity analyses suggested that the observed benefit in women was heavily influenced by results from two individual clinical trials.

Clinical Impact:

This analysis confirms that both male and female patients should continue to receive first-line chemo-immunotherapy for advanced ESCC, as survival improves in both groups. However, the findings also emphasise that biological sex should be considered as an important variable in future immunotherapy research. Larger studies incorporating translational biomarkers may clarify whether sex-related differences in immune biology can eventually guide treatment personalisation.

Bottom Line:

Chemotherapy combined with immune checkpoint inhibitors improves survival in both men and women with advanced oesophagal squamous cell carcinoma. Although the survival benefit appears greater in men, current evidence does not support altering treatment based on sex alone. Future clinical trials should routinely evaluate biological sex as a key factor influencing immunotherapy outcomes.