David M O'Malley1, Giovanni Mendonca Bariani2, Philippe A Cassier3, Aurelien Marabelle4, Aaron R Hansen5, Ana De Jesus Acosta6, Wilson H Miller7,8, Tamar Safra9,10, Antoine Italiano11,12, Linda Mileshkin13, Lei Xu14, Fan Jin14, Kevin Norwood14, Michele Maio15. 1. Division of Gynecologic Oncology, The Ohio State University Wexner Medical Center and The James Comprehensive Cancer Center, Columbus, OH. 2. Department of Medical Oncology, Instituto do Câncer do Estado de São Paulo, Universidade de São Paulo, São Paulo, Brazil. 3. Department of Medical Oncology, Centre Léon Bérard, Lyon, France. 4. Département d'Innovation Thérapeutique et d'Essais Précoces (DITEP), Institut National de la Santé et de la Recherche Médicale (INSERM U1015), Gustave Roussy, Université Paris Saclay, Villejuif, France. 5. Division of Medical Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada. 6. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD. 7. Segal Cancer Centre, Jewish General Hospital, Rossy Cancer Network, Montreal, QC, Canada. 8. Departments of Oncology and Medicine, McGill University, Montreal, QC, Canada. 9. Oncology Department, Tel Aviv Medical Center, Tel Aviv, Israel. 10. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. 11. Early Phase Trials and Sarcoma Units, Institut Bergonie, Bordeaux, France. 12. Faculty of Medicine, University of Bordeaux, France. 13. Peter MacCallum Cancer Centre and the Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia. 14. Merck & Co, Inc, Kenilworth, NJ. 15. Division of Medical Oncology and Immunotherapy, Center for Immuno-Oncology, Department of Oncology, University Hospital of Siena, Siena, Italy.
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.
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.
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