Comparative analysis of systemic treatment with or without immune checkpoint inhibitors for advanced or recurrent endometrial cancer: A systematic review and meta-analysis of randomized controlled trials

Abstract

Background: Immune checkpoint inhibitors (ICIs) have revolutionized gynecologic oncology, but their value in endometrial cancer remains unclear. We conducted this systematic review and meta-analysis to evaluate the efficacy and safety of ICIs in combination with systemic treatment in this setting.

Methods: We searched phase II and III randomized controlled trials comparing systemic therapy with or without ICIs for advanced or recurrent endometrial cancer. We conducted this meta-analysis in two stages, first evaluating any therapy with or without ICIs, then a comparison of chemotherapy alone or with ICIs only. The primary objective of our analysis was to evaluate progression-free survival (PFS) and overall survival (OS). Hazard ratios (HRs) were pooled using random-effects models. Individual patient data were reconstructed from Kaplan-Meier curves for further survival analysis. This meta-analysis is registered in PROSPERO (CRD42025649698).

Results: Six trials with a total of 3826 patients were included in this meta-analysis. In the intention-to-treat population, ICIs improved PFS with HR 0.71 [0.63; 0.81] 95 % confidence interval (95 % CI), p < 0.00001 and OS HR 0.79 [0.68; 0.93], p = 0.004. For dMMR patients, the benefit was pronounced for PFS, HR 0.40 [0.32; 0.49], p < 0.00001 and OS, HR 0.44 [0.33; 0.57], p < 0.00001. For pMMR patients, PFS was improved with HR 0.76, p = 0.002, but no survival benefit with HR at 0.90, p = 0.18.

Conclusion: The addition of ICIs to chemotherapy for advanced or recurrent endometrial cancer significantly improves outcomes, especially for patients with a dMMR profile. For pMMR patients, the gain in PFS was evident, but OS remained immature.

Keywords: Endometrial cancer; Immune checkpoint inhibitors; Meta-analysis.