Combination of immunotherapy and chemotherapy as first-line treatment for advanced or recurrent endometrial cancer: a meta-analysis of phase 3 trials

TL;DR

Combining immunotherapy with chemotherapy improves outcomes for advanced or recurrent endometrial cancer, with better survival and response rates.

Contribution

A meta-analysis showing that immunotherapy plus chemotherapy outperforms chemotherapy alone in treating advanced or recurrent endometrial cancer.

Findings

Combination therapy improved progression-free and overall survival compared to chemotherapy alone.

Objective response rates increased with the combination treatment.

Greater benefits were observed in dMMR, PD-L1-positive, and recurrent disease subgroups.

Abstract

The integration of immunotherapy with chemotherapy (CT) has emerged as a major focus of clinical research in recent years for patients with advanced or recurrent endometrial cancer (EC). Recent phase 3 randomized controlled trials (RCTs) have reported heterogeneous outcomes, prompting ongoing debate within the oncology community. This study aimed to evaluate the efficacy and safety of this combined approach through a meta-analysis of phase 3 RCTs.

A systematic literature search identified phase 3 RCTs comparing first-line immunotherapy plus CT versus CT alone in advanced or recurrent EC. Meta-analyses were performed to pool hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS), odds ratios (ORs) for objective response rate (ORR), and relative risks (RRs) for adverse events (AEs).

Four phase 3 RCTs (n = 2,334) met eligibility criteria. The combination therapy significantly improved PFS (HR, 0.60; 95% CI, 0.47–0.78), OS (HR, 0.75; 95% CI, 0.65–0.87), and ORR (OR, 1.42; 95% CI, 1.17–1.73) compared to CT alone. While a modest increase in grade 3–5 AEs (RR, 1.11; 95% CI, 1.03–1.20) was observed with combination therapy, there was no significant rise in serious AEs. Subgroup analyses revealed enhanced survival benefits in patients with mismatch repair-deficient (dMMR) tumors, PD-L1-positive tumors, and recurrent disease.

This meta-analysis demonstrates that combining immunotherapy with CT as first-line treatment for advanced or recurrent EC offers superior efficacy over CT alone while maintaining a comparable toxicity profile. Notably, greater benefits were observed in dMMR, PD-L1-positive, and recurrent disease subgroups.

The online version contains supplementary material available at 10.1186/s12885-025-15039-2.

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