Efficacy of immune-checkpoint inhibitors combined with cytotoxic chemotherapy in advanced or recurrent endometrial cancer: A systematic review and meta-analysis

Background The combination of immune checkpoint inhibitors (ICIs) and platinum-based chemotherapy has emerged as a highly promising primary option for advanced or recurrent endometrial cancer (EC). The study aimed to evaluate treatment efficacy of ICIs with cytotoxic chemotherapy in EC. Methods We conducted a comprehensive review of randomized controlled trials up to November 11, 2023, focusing on immunotherapy combined with chemotherapy versus chemotherapy alone for EC. The primary endpoint was the pooled hazard ratio (HR), which was further analyzed across subgroups based on mismatch repair (MMR) status, race, histology, and programmed death-ligand 1 (PD-L1) status. The protocol was registered in PROSPERO (CRD42023475669). Findings Four trials with 2335 patients were analyzed. ICIs with chemotherapy significantly prolonged progression-free survival (PFS) (HR, 0.70; 95% CI, 0.62–0.79) and overall survival (OS) (HR, 0.75; 95% CI, 0.63–0.89) compared to chemotherapy alone. Stratification by MMR status showed substantial benefits for dMMR (PFS; HR, 0.33; 95% CI, 0.26–0.43; OS; HR, 0.37; 95% CI, 0.22–0.91) over pMMR cohorts in both PFS and OS. In the subgroup analysis, there was significant PFS advantage in Caucasian (HR, 0.63; 95% CI, 0.54–0.72) over non-Caucasian, in endometrioid histology (HR, 0.66; 95% CI, 0.56–0.78) over non-endometrioid, and in PD-L1 positive (HR, 0.39; 95% CI, 0.19–0.81) over PD-L1 negative population. Interpretation ICIs combined with platinum-based chemotherapy significantly prolonged PFS and OS in patients with advanced or recurrent EC. Patients with dMMR status, Caucasians, endometrioid histology, and positive PD-L1 status showed significant PFS benefits, emphasizing the need for personalized treatment approaches to improve outcomes.