PD-1/PD-L1 inhibitors plus chemotherapy improve survival in advanced endometrial cancer

Photo by Trust "Tru" Katsande / Unsplash

Frontiers in Medicine Published June 2, 2026 Medically reviewed June 2, 2026 DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Consider PD-1/PD-L1 inhibitors plus chemotherapy for first-line advanced endometrial cancer, especially in dMMR.

This systematic review and meta-analysis of randomized controlled trials evaluated the efficacy of PD-1/PD-L1 inhibitors plus chemotherapy versus chemotherapy alone as first-line therapy for advanced or metastatic endometrial cancer. The analysis included 4,052 patients (2,109 in the combination arm and 1,943 in the chemotherapy-alone arm).

Key findings showed that the combination improved overall survival (median 43.7 vs 29.1 months) and progression-free survival (median 14.6 vs 10.2 months), both favoring the combination. Objective response rate was also higher (RR 1.10, 95% CI 1.02–1.18). Complete response was significantly improved (RR 1.60, 95% CI 1.25–2.05), while partial response showed no significant difference (RR 0.99, 95% CI 0.88–1.12). Stable disease was less likely with combination (RR 0.68, 95% CI 0.54–0.86), and progressive disease did not differ significantly (RR 0.69, 95% CI 0.45–1.06).

Common adverse events included fatigue, alopecia, nausea, peripheral neuropathy, anemia, arthralgia, constipation, and diarrhea. The authors note that the significant OS benefit was observed in dMMR tumors, while pMMR tumors showed PFS benefit but no OS benefit. Limitations were not reported in the source. Clinicians should interpret these pooled results cautiously, as individual trial details are not provided.

Study Details

Study typeMeta analysis

EvidenceLevel 1

PublishedJun 2026

View Original Abstract ↓

ObjectiveTo 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.MethodsA 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.ResultsTen 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.ConclusionThe 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 Registrationhttps://www.crd.york.ac.uk/PROSPERO/view/, identifier CRD420251271038.