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

被引：316

作者：

O'Malley, David M. ^{[1
,2
]}

Bariani, Giovanni Mendonca ^{[3
]}

Cassier, Philippe A. ^{[4
]}

Marabelle, Aurelien ^{[5
]}

Hansen, Aaron R. ^{[6
]}

Acosta, Ana De Jesus ^{[7
]}

Miller, Wilson H., Jr. ^{[8
,9
,10
]}

Safra, Tamar ^{[11
,12
]}

Italiano, Antoine ^{[13
,14
,15
]}

Mileshkin, Linda ^{[16
,17
]}

Xu, Lei ^{[18
]}

Jin, Fan ^{[18
]}

Norwood, Kevin ^{[18
]}

Maio, Michele ^{[19
]}

机构：

[1] Ohio State Univ, Div Gynecol Oncol, Wexner Med Ctr, 320 West 10th Ave, Columbus, OH 43210 USA

[2] James Comprehens Canc Ctr, 320 West 10th Ave, Columbus, OH 43210 USA

[3] Univ Sao Paulo, Inst Canc Estado Sao Paulo, Dept Med Oncol, Sao Paulo, Brazil

[4] Ctr Leon Berard, Dept Med Oncol, Lyon, France

[5] Univ Paris Saclay, Inst Natl Sante & Rech Med INSERM, Dept Innovat Therapeut & Essais Precoces DITEP, U1015,Gustave Roussy, Villejuif, France

[6] Princess Margaret Canc Ctr, Div Med Oncol, Toronto, ON, Canada

[7] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA

[8] Jewish Gen Hosp, Segal Canc Ctr, Rossy Canc Network, Montreal, PQ, Canada

[9] McGill Univ, Dept Oncol, Montreal, PQ, Canada

[10] McGill Univ, Dept Med, Montreal, PQ, Canada

[11] Tel Aviv Med Ctr & Sch Med, Oncol Dept, Tel Aviv, Israel

[12] Tel Aviv Univ, Sackler Sch Med, Tel Aviv, Israel

[13] Inst Bergonie, Early Phase Trials Unit, Bordeaux, France

[14] Inst Bergonie, Sarcoma Unit, Bordeaux, France

[15] Univ Bordeaux, Fac Med, Bordeaux, France

[16] Univ Melbourne, Peter MacCallum Canc Ctr, Melbourne, Vic, Australia

[17] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia

[18] Merck & Co Inc, Kenilworth, NJ USA

[19] Univ Hosp Siena, Ctr Immunooncol, Dept Oncol, Div Med Oncol & Immunotherapy, Siena, Italy

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2022年 / 40卷 / 07期

关键词：

PD-1; EXPRESSION; TUMORS;

D O I：

10.1200/JCO.21.01874

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

PURPOSE Pembrolizumab demonstrated durable antitumor activity in patients with previously treated, advanced microsatellite instability-high or mismatch repair-deficient (MSI-H/d MMR) 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/d MMR 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 rad iologic 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. (C) 2022 by American Society of Clinical Oncology

引用

页码：752 / 761

页数：11

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