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Ref Type Journal Article
PMID (34990208)
Authors O'Malley DM, Bariani GM, Cassier PA, Marabelle A, Hansen AR, De Jesus Acosta A, Miller WH, Safra T, Italiano A, Mileshkin L, Xu L, Jin F, Norwood K, Maio M
Title Pembrolizumab in Patients With Microsatellite Instability-High Advanced Endometrial Cancer: Results From the KEYNOTE-158 Study.
Journal Vol Issue Date Pages Journal Short Title
Journal of clinical oncology : official journal of the American Society of Clinical Oncology 40 7 2022 03 01 752-761 J Clin Oncol
URL
Abstract Text 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.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.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).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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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
MLH1 negative endometrial carcinoma sensitive Pembrolizumab FDA approved - On Companion Diagnostic Actionable In a Phase II trial (KEYNOTE-158) that supported FDA approval, Keytruda (pembrolizumab) treatment resulted in an objective response rate of 48% (38/79, 11 complete responses, 27 partial responses) in patients with advanced microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) endometrial carcinoma, with a median progression-free survival of 13.1 months (PMID: 34990208; NCT02628067). detail... 34990208 detail...
MSH6 negative endometrial carcinoma sensitive Pembrolizumab FDA approved - On Companion Diagnostic Actionable In a Phase II trial (KEYNOTE-158) that supported FDA approval, Keytruda (pembrolizumab) treatment resulted in an objective response rate of 48% (38/79, 11 complete responses, 27 partial responses) in patients with advanced microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR, often defined by the loss of MLH1, PMS2, MSH2, or MSH6 expression by IHC) endometrial carcinoma, with a median progression-free survival of 13.1 months (PMID: 34990208; NCT02628067). detail... detail... 34990208