As reported in the Journal of Clinical Oncology by David M. O’Malley, MD, and colleagues, pembrolizumab showed durable activity in a cohort of patients with microsatellite instability–high or mismatch repair–deficient (MSI-H/dMMR) advanced endometrial cancer enrolled in the multicohort KEYNOTE-158 study.

David M. O’Malley, MD

Study Details

The cohort included 90 patients with previously treated advanced disease enrolled from sites in 15 countries between February 2016 and September 2020. Patients received pembrolizumab at 200 mg every 3 weeks for 35 cycles. The primary endpoint was objective response rate according to Response Evaluation Criteria in Solid Tumors version 1.1 on independent central radiologic review.

Key Findings

As of October 2020, 18 (20%) of 90 treated patients had completed 35 cycles of pembrolizumab and 52 (58%) had discontinued treatment. In the efficacy population (consisting of 79 patients who received at least one dose of pembrolizumab and had 26 weeks or longer of follow-up), median time from first dose to data cutoff was 42.6 months (range = 6.4–56.1 months).

Objective response was observed in 38 of 79 patients (48%, 95% confidence interval [CI] = 37%–60%), including complete response in 11 (14%); an additional 14 patients (18%) had stable disease. Objective response rates were 53% (95% CI = 36%–69%) among 38 patients who had received one prior line of therapy and 44% (95% CI = 28%–60%) among 41 who had received two or more prior lines.

Median time to response was 2.3 months (range = 1.3–10.6 months). Median response duration was not reached (range = 2.9–49.7+ months); estimated proportions of responses persisting for ≥ 1, 2, and 3 years were 88%, 73%, and 68%.

Median progression-free survival was 13.1 months (95% CI = 4.3–34.4 months), with estimated rates of 51% at 1 year, 41% at 2 years, and 37% at 3 and 4 years. Median overall survival was not reached (95% CI = 27.2 months–not reached), with estimated rates of 69% at 1 year, 64% at 2 years, and 60% at 3 and 4 years.

Among 90 patients in the safety analysis, the most common treatment-related adverse events of any grade were pruritus (24%), fatigue (21%), and diarrhea (16%). Grade 3 or 4 treatment-related adverse events occurred in 12% of patients (hyperglycemia, decreased lymphocytes, and increased transaminases in two or more patients). Treatment-related adverse events led to discontinuation in 7% of patients. Immune-mediated adverse events or infusion reactions occurred in 28% (grade 3 or 4 in 7%). No treated-related deaths occurred.

The investigators concluded, “Pembrolizumab demonstrated robust and durable antitumor activity and encouraging survival outcomes with manageable toxicity in patients with previously treated, advanced MSI-H/dMMR endometrial cancer.”

Dr. O’Malley, of The Ohio State University Wexner Medical Center and The James Comprehensive Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc. For full disclosures of the study authors, visit ascopubs.org.