Pembrolizumab or Placebo Plus Adjuvant Chemotherapy With or Without Radiotherapy for Newly Diagnosed, High-Risk Endometrial Cancer: Results in Mismatch Repair-Deficient Tumors
Abstract
Mismatch repair-deficient (dMMR) endometrial cancer (EC) is an inflamed phenotype with poor outcomes when meeting high-risk criteria and limited treatment options in the adjuvant setting. We report protocol-prespecified subgroup analysis of patients with dMMR tumors from the phase III ENGOT-en11/GOG-3053/KEYNOTE-B21 study (ClinicalTrials.gov identifier: NCT04634877 ) in newly diagnosed, high-risk EC after surgery with curative intent. Patients were randomly assigned to pembrolizumab 200 mg or placebo (six cycles) plus carboplatin-paclitaxel (four to six cycles) once every 3 weeks, then pembrolizumab 400 mg or placebo once every 6 weeks (six cycles), respectively. MMR status was a stratification factor. Patients received radiotherapy at investigator discretion. Investigator-assessed disease-free survival (DFS) was a primary end point. No formal hypothesis testing was performed for subgroup analysis. In the intention-to-treat population, 141 patients in the pembrolizumab arm and 140 in the placebo arm had dMMR tumors. At this interim analysis, hazard ratio for DFS favored pembrolizumab (0.31 [95% CI, 0.14 to 0.69]); median DFS was not reached in either group. Two-year DFS rates were 92.4% (95% CI, 84.4 to 96.4) and 80.2% (95% CI, 70.8 to 86.9), respectively. No new safety signals occurred. Longer-term follow-up of outcomes will be evaluated at final analysis. Preplanned subgroup analysis on the basis of the study's stratification factors suggests that pembrolizumab plus chemotherapy improves DFS and is clinically relevant for patients with dMMR tumors in the curative-intent setting.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (30)
Brian M. Slomovitz
Gynecologic Oncology, Mount Sinai Medical Center, Miami Beach, FL
David Cibula
Weiguo Lv
Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China
Fırat Ortaç
Ankara University School of Medicine, Ankara, Turkey
Sakari Hietanen
Turku University Hospital and NSGO-CTU, Turku, Finland
Floor Backes
The Ohio State University Comprehensive Cancer Center, Columbus, OH
Akira Kikuchi
Domenica Lorusso
Gynecology Oncology Program Humanitas University San Pio X Milan Italy
Anna Danska-Bidzinska
Vanessa Samouëlian
Gynecologic Oncology, Centre Hospitalier de l’Université de Montréal (CHUM), Centre de Recherche de l’Université de Montréal (CRCHUM), Université de Montréal, Montreal, QC, Canada
Maria-Pilar Barretina-Ginesta
Grupo Español de Investigación en Cáncer de Ovario (GEICO) and Medical Oncology Department, Institut Català d´Oncologia (ICO), Girona, Spain
Christof Vulsteke
Integrated Cancer Center Ghent, AZ Maria Middelares, Ghent, Belgium
Chyong-Huey Lai
Gynecologic Cancer Research Center, Taoyuan City, Taiwan
Bhavana Pothuri
Division of Gynecologic Oncology, Laura & Isaac Perlmutter Cancer Center, NYU Langone Health, New York, NY
Yu Zhang
Xiangya Hospital, Central South University Changsha China
Manuel Magallanes-Maciel
Centro Oncologico Internacional, Mexico City, Mexico
Amnon Amit
Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
Valentina Guarneri
Veneto Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico, Padua, Italy
Flora Zagouri
Alexandra Hospital, Athens, Greece
Maria Bell
Julia Welz
Gemma Eminowicz
Martin Hruda
Central and Eastern European Gynecologic Oncology Group (CEEGOG), Prague, Czech Republic
Lyndsay J. Willmott
GOG Foundation, Philadelphia, PA
Jasmine Lichfield
Astellas Pharma Europe Ltd, Addlestone, United Kingdom
Wei Wang
Robert Orlowski
University of Texas M.D. Anderson Cancer Center, Houston
Gursel Aktan
Merck & Co, Inc, Rahway, NJ
Laurence Gladieff
Toon Van Gorp