Does Pembrolizumab Improve Disease-Free Survival in Mismatch Repair-Deficient Endometrial Cancer?

A phase 3 subgroup analysis found that pembrolizumab combined with carboplatin-paclitaxel chemotherapy improved 2-year disease-free survival (92.4% vs 80.2%) in patients with mismatch repair-deficient (dMMR) endometrial cancer (EC) at high risk of recurrence.

Patients with dMMR tumors, which are characterized by high tumor mutational burden and immunogenicity, often have poorer outcomes compared with mismatch repair-proficient tumors despite similar standard-of-care treatments. This study aimed to address the need for improved adjuvant strategies in this high-risk population.

The study included 281 patients with dMMR tumors, randomly assigned to receive either pembrolizumab or placebo in addition to chemotherapy, with radiotherapy administered at the investigator’s discretion. The primary endpoint was disease-free survival (DFS).

At the interim analysis, DFS favored pembrolizumab over placebo, with a hazard ratio of 0.31 (95% CI, 0.14–0.69). The two-year DFS rates were 92.4% for pembrolizumab versus 80.2% for placebo, with median DFS not reached in either group. Fewer recurrences were reported in the pembrolizumab group (three investigator-assessed recurrences vs 23 in the placebo group). Safety findings were consistent with known profiles of pembrolizumab and chemotherapy, with no new safety signals identified.

“Our data suggest a clinically relevant improvement in DFS when pembrolizumab is added to standard care for the dMMR subgroup, a well-established biomarker based on biology,” the authors concluded.

Reference

Slomovitz BM, Cibula D, Lv W, et al. Pembrolizumab or placebo plus adjuvant chemotherapy with or without radiotherapy for newly diagnosed, high-risk endometrial cancer: results in mismatch repair-deficient tumors. J Clin Oncol. 2025;43(3):251-259. doi:10.1200/JCO-24-01887