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.

Ankara University School of Medicine Ankara Turkey

Arizona Center for Cancer Care Phoenix AZ

Belgium and Luxembourg Gynaecological Oncology Group Leuven Belgium

Catalan Institute of Oncology and Girona Biomedical Research Institute Medical School University of Girona Girona Spain

Central and Eastern European Gynecologic Oncology Group Prague Czech Republic

Centro Oncologico Internacional Mexico City Mexico

Creighton University School of Medicine at Dignity Health St Joseph's Hospital and Medical Center Phoenix AZ

Department of Clinical Therapeutics Medical School of National and Kapodistrian University of Athens Alexandra General Hospital of Athens Athens Greece

Department of Gynecologic Oncology Women's Hospital School of Medicine Zhejiang University Hangzhou Zhejiang China

Department of Gynecological Oncology 2nd Division of Obstetrics and Gynecology Medical University of Warsaw Warsaw Poland

Department of Gynecology and Gynecologic Oncology Evang Kliniken Essen Mitte Essen Germany

Department of Gynecology and Obstetrics University Hospital Kralovske Vinohrady and 3rd Faculty of Medicine Charles University Prague Czech Republic

Department of Gynecology Niigata Cancer Center Hospital Niigata Japan

Department of Gynecology Obstetrics and Neonatology General University Hospital Prague 1st Faculty of Medicine Charles University Prague Czech Republic

Department of Gynecology Xiangya Hospital Central South University Changsha Hunan PR China

Department of Obstetrics and Gynecology and Medicine Division of Gynecologic Oncology Perlmutter Cancer Center NYU Langone Health New York NY

Department of Obstetrics and Gynecology Chang Gung Memorial Hospital Linkou Branch Chang Gung University College of Medicine Taoyuan Taiwan

Department of Obstetrics and Gynecology Rambam Health Care Campus Haifa Israel

Department of Surgery Oncology and Gastroenterology University of Padova Padova Italy

Division of Gynaecological Oncology University Hospital Leuven Leuven Cancer Institute Leuven Belgium

Division of Gynecologic Oncology Ohio State University and James Cancer Hospital Columbus OH

Faculty of Medicine Technion Israel Institute of Technology Haifa Israel

Fondazione Policlinico Universitario A Gemelli IRCCS Rome and Humanitas University Rozzano Italy

German Gynecological Oncology Group Essen Germany

GOG Foundation Philadelphia PA

Gynecologic Cancer Research Center Chang Gung Memorial Hospital Linkou Branch Taiwan

Gynecologic Oncology Centre Hospitalier de l'Université de Montréal Université de Montréal Montreal QC Canada

Hellenic Cooperative Oncology Group Athens Greece

Integrated Cancer Center Ghent Department of Medical Oncology AZ Maria Middelares Ghent and Center of Oncological Research University of Antwerp Wilrijk Antwerp Belgium

Israeli Society of Gynecology Oncology Israel

Maricopa Integrated Health System Phoenix AZ

Mario Negri Gynecologic Oncology Milan Italy

Medical Oncology 2 Istituto Oncologico Veneto IOV IRCCS Padova Italy

Medical Oncology Oncopole CLAUDIUS REGAUD IUCT Oncopole Toulouse France

Merck and Co Inc Rahway NJ

Mount Sinai Medical Center Miami Beach FL

MSD China Beijing China

MSD UK London United Kingdom

Multicenter Italian Trials in Ovarian Cancer and Gynecologic Malignancies Rome Italy

National Cancer Research Institute London United Kingdom

National Investigators Group for the Study of Ovarian and Breast Cancers Paris France

Nordic Society of Gynaecological Oncology Copenhagen Denmark

Polish Group of Gynaecological Oncology Warsaw Poland

Sanford Health Sioux Falls SD

Spanish Ovarian Cancer Research Group Madrid Spain

Taiwanese Gynecologic Oncology Group Taoyuan Taiwan

The University of Arizona College of Medicine Phoenix AZ

Turkish Society of Gynecologic Oncology Istanbul Turkey

Turku University Hospital FICAN West Cancer Centre Turku Finland

University College London Hospitals and University College London London United Kingdom

J Clin Oncol. 2025 Feb 10;43(5):623. doi: 10.1200/JCO-24-02691. PubMed

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ClinicalTrials.gov
NCT04634877