Pembrolizumab or Placebo Plus Adjuvant Chemotherapy With or Without Radiotherapy for Newly Diagnosed, High-Risk Endometrial Cancer: Results in Mismatch Repair-Deficient Tumors

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.

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Publication Details

Journal
Journal of Clinical Oncology
Published
2024-10-16
DOI
https://doi.org/10.1200/jco-24-01887
Citations
19
Primary Topic
Genetic factors in colorectal cancer
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article
Field-Weighted Citation Impact
8.07
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article

Pembrolizumab or Placebo Plus Adjuvant Chemotherapy With or Without Radiotherapy for Newly Diagnosed, High-Risk Endometrial Cancer: Results in Mismatch Repair-Deficient Tumors

Floor Jenniskens Backes, Laurence Gladieff, Bhavana Pothuri, Lyndsay Willmott et al.
19 citations
Journal of Clinical Oncology
Genetic factors in colorectal cancer
8.07
article

Pembrolizumab or Placebo Plus Adjuvant Chemotherapy With or Without Radiotherapy for Newly Diagnosed, High-Risk Endometrial Cancer: Results in Mismatch Repair-Deficient Tumors

Floor Jenniskens Backes, Laurence Gladieff, Bhavana Pothuri, Lyndsay Willmott, Christof Vulsteke, Anna Dańska-Bidzińska, Gursel Aktan, Valentina Guarneri, Brian M. Slomovitz, Manuel Magallanes-Maciel, Maria-Pilar Barretina-Ginesta, Martin Hruda, Weiguo Lv, Robert Orlowski, Fırat Ortaç, Chyong‐Huey Lai, Vanessa Samouëlian, Domenica Lorusso, Gemma Eminowicz, David Cibula, Toon Van Gorp, Jasmine Lichfield, Akira Kikuchi, Julia Welz, Liang Yu, Amnon Amit, Maria C. Bell, Sakari Hietanen, Flora Zagouri, Wei Wang
article en
19 citations

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.

Journal of Clinical OncologyVol. 43(3)
Creighton University (US), Gynecologic Oncology Group (US), Merck & Co., Inc., Rahway, NJ, USA (United States) (US), Sanford Health (US), St. Joseph's Hospital and Medical Center (US), Humanitas University (IT), University of Arizona (US), University of Padua (IT), Central South University (CN), University of Antwerp (BE), Ankara University (TR), Chang Gung University (TW), Technion – Israel Institute of Technology (IL), Mario Negri Institute for Pharmacological Research (IT), National and Kapodistrian University of Athens (GR), Charles University (CZ), Universitat de Girona (ES), Medical University of Warsaw (PL), The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (US), Royal London Hospital (GB), Rambam Health Care Campus (IL), Turku University Hospital (FI), Agostino Gemelli University Polyclinic (IT), Pancreatic Cancer Action Network (US), Dignity Health (US), Chang Gung Memorial Hospital (TW), NYU Langone Health (US), MSD (UK) Limited (United Kingdom) (GB), Nordic Society of Gynecologic Oncology (DK), The European Academy of Gynaecological Surgery (BE), Niigata Cancer Center Hospital (JP), Mount Sinai Medical Center (US), Institut Català d'Oncologia (ES), Istituto Oncologico Veneto (IT), Alexandra Hospital (GR), Hellenic Cooperative Oncology Group (GR), Linkou Chang Gung Memorial Hospital (TW), Institut Claudius Regaud (FR), Women's Hospital, School of Medicine, Zhejiang University (CN), Centre Hospitalier de l’Université de Montréal (CA), AZ Maria Middelares (BE), Kliniken Essen-Mitte (DE), Valleywise Health (US), Istituti di Ricovero e Cura a Carattere Scientifico (IT), St. Joseph's Hospital (US), Spanish Ovarian Cancer Research Group (ES), University Hospital Kralovske Vinohrady (CZ), Xiangya Hospital Central South University (CN), General University Hospital in Prague (CZ), University College London (GB), National Cancer Research Institute (GB), Companhia Energética de Minas Gerais (Brazil) (BR), KU Leuven (BE)
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Openalex Percentile: Top 2%
Genetic factors in colorectal cancer
8.07
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