PD-1/PD-L1 inhibitors plus chemotherapy as first-line therapy for advanced or metastatic endometrial cancer: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE

To evaluate the efficacy and safety of programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors combined with chemotherapy as first-line treatment for advanced or metastatic endometrial cancer.

METHODS

A systematic literature search was conducted in PubMed, Embase, Web of Science, the Cochrane Library, and ClinicalTrials.gov from inception to November 26, 2025. Meta-analyses were performed to pool outcomes including progression-free survival, overall survival, objective response rate, complete response, partial response, stable disease, progressive disease, and treatment-related adverse events.

RESULTS

Ten randomized controlled trials encompassing 4,052 patients were included (combination arm: n=2,109; chemotherapy-alone arm: n=1,943). Compared with chemotherapy alone, the addition of PD-1/PD-L1 inhibitors significantly prolonged median overall survival (43.7 vs. 29.1 months) and median progression-free survival (14.6 vs. 10.2 months). The relative risks (RR) for efficacy endpoints were as follows: complete response, 1.60 (95% CI: 1.25-2.05); partial response, 0.99 (95% CI: 0.88-1.12); stable disease, 0.68 (95% CI: 0.54-0.86); progressive disease, 0.69 (95% CI: 0.45-1.06); and objective response rate, 1.10 (95% CI: 1.02-1.18). The most common treatment-related adverse events were fatigue, alopecia, nausea, peripheral neuropathy, anemia, arthralgia, constipation, and diarrhea.

CONCLUSION

The combination of PD-1/PD-L1 inhibitors and chemotherapy significantly improves progression-free survival and overall survival in patients with advanced or metastatic endometrial cancer, with the significant OS benefit in dMMR; PFS benefit but no OS benefit in pMMR.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/, identifier CRD420251271038.