Pembrolizumab in Patients With Microsatellite Instability-High Advanced Endometrial Cancer: Results From the KEYNOTE-158 Study
- Author(s)
- O'Malley, DM; Bariani, GM; Cassier, PA; Marabelle, A; Hansen, AR; De Jesus Acosta, A; Miller, WH, Jr; Safra, T; Italiano, A; Mileshkin, L; Xu, L; Jin, F; Norwood, K; Maio, M;
- Details
- Publication Year 2022-03-01,Volume 40,Issue #7,Page 752-761
- Journal Title
- Journal of Clinical Oncology
- Publication Type
- Research article
- Abstract
- PURPOSE: Pembrolizumab demonstrated durable antitumor activity in patients with previously treated, advanced microsatellite instability-high or mismatch repair-deficient (MSI-H/dMMR) tumors, including endometrial cancer, in the nonrandomized, open-label, multicohort, phase II KEYNOTE-158 study (NCT02628067). We report efficacy and safety outcomes for patients with MSI-H/dMMR endometrial cancer enrolled in KEYNOTE-158. METHODS: Eligible patients from cohorts D (endometrial cancer, regardless of MSI-H/dMMR status) and K (any MSI-H/dMMR solid tumor, except colorectal) with previously treated, advanced MSI-H/dMMR endometrial cancer received pembrolizumab 200 mg once every 3 weeks for 35 cycles. The primary end point was objective response rate per RECIST version 1.1 by independent central radiologic review. Secondary end points included duration of response, progression-free survival, overall survival, and safety. RESULTS: As of October 5, 2020, 18 of 90 treated patients (20%) had completed 35 cycles of pembrolizumab and 52 (58%) had discontinued treatment. In the efficacy population (patients who received >/= 1 dose of pembrolizumab and had >/= 26 weeks of follow-up; N = 79), the median time from first dose to data cutoff was 42.6 (range, 6.4-56.1) months. The objective response rate was 48% (95% CI, 37 to 60), and median duration of response was not reached (2.9-49.7+ months). Median progression-free survival was 13.1 (95% CI, 4.3 to 34.4) months, and median overall survival was not reached (95% CI, 27.2 months to not reached). Among all treated patients, 76% had >/= 1 treatment-related adverse event (grades 3-4, 12%). There were no fatal treatment-related events. Immune-mediated adverse events or infusion reactions occurred in 28% of patients (grades 3-4, 7%; no fatal events). CONCLUSION: 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.
- Keywords
- Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized/*therapeutic use; Antineoplastic Agents, Immunological/*therapeutic use; Biomarkers, Tumor/*genetics; *DNA Mismatch Repair; Endometrial Neoplasms/*drug therapy/genetics/pathology; Female; Follow-Up Studies; Humans; *Microsatellite Instability; Middle Aged; Non-Randomized Controlled Trials as Topic; Prognosis; Retrospective Studies; Survival Rate
- Department(s)
- Medical Oncology
- PubMed ID
- 34990208
- Publisher's Version
- https://doi.org/10.1200/JCO.21.01874
- Open Access at Publisher's Site
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Creation Date: 2025-02-14 04:06:04
Last Modified: 2025-02-14 04:08:15