Pembrolizumab in Patients With Microsatellite Instability-High Advanced Endometrial Cancer: Results From the KEYNOTE-158 Study

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)....

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Veröffentlicht in:Journal of clinical oncology Jg. 40; H. 7; S. 752
Hauptverfasser: O'Malley, David M, Bariani, Giovanni Mendonca, Cassier, Philippe A, Marabelle, Aurelien, Hansen, Aaron R, De Jesus Acosta, Ana, Miller, Jr, Wilson H, Safra, Tamar, Italiano, Antoine, Mileshkin, Linda, Xu, Lei, Jin, Fan, Norwood, Kevin, Maio, Michele
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 01.03.2022
Schlagworte:
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
Endometrial Neoplasms - genetics
Endometrial Neoplasms - pathology
Female
Follow-Up Studies
Humans
Microsatellite Instability
Middle Aged
Non-Randomized Controlled Trials as Topic
Prognosis
Retrospective Studies
Survival Rate
ISSN:1527-7755, 1527-7755
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Zusammenfassung: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.
Bibliographie:ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
content type line 23
ISSN:1527-7755
1527-7755
DOI:10.1200/JCO.21.01874