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Pembrolizumab or Placebo Plus Adjuvant Chemotherapy With or Without Radiotherapy for Newly Diagnosed, High-Risk Endometrial Cancer: Results in Mismatch Repair-Deficient Tumors
BM. Slomovitz, D. Cibula, W. Lv, F. Ortaç, S. Hietanen, F. Backes, A. Kikuchi, D. Lorusso, A. Dańska-Bidzińska, V. Samouëlian, MP. Barretina-Ginesta, C. Vulsteke, CH. Lai, B. Pothuri, Y. Zhang, M. Magallanes-Maciel, A. Amit, V. Guarneri, F....
Language English Country United States
Document type Journal Article, Randomized Controlled Trial, Clinical Trial, Phase III, Multicenter Study
PubMed
39411812
DOI
10.1200/jco-24-01887
Knihovny.cz E-resources
- MeSH
- Chemotherapy, Adjuvant MeSH
- Adult MeSH
- Double-Blind Method MeSH
- Antibodies, Monoclonal, Humanized * therapeutic use administration & dosage adverse effects MeSH
- Carboplatin administration & dosage MeSH
- Middle Aged MeSH
- Humans MeSH
- Endometrial Neoplasms * pathology drug therapy mortality therapy MeSH
- DNA Mismatch Repair * MeSH
- Paclitaxel * administration & dosage MeSH
- Disease-Free Survival MeSH
- Antineoplastic Combined Chemotherapy Protocols * therapeutic use MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
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
Central and Eastern European Gynecologic Oncology Group Prague Czech Republic
Centro Oncologico Internacional Mexico City Mexico
Department of Gynecology and Gynecologic Oncology Evang Kliniken Essen Mitte Essen Germany
Department of Gynecology Niigata Cancer Center Hospital Niigata Japan
Department of Gynecology Xiangya Hospital Central South University Changsha Hunan PR China
Department of Obstetrics and Gynecology Rambam Health Care Campus Haifa Israel
Department of Surgery Oncology and Gastroenterology University of Padova Padova Italy
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
Hellenic Cooperative Oncology Group Athens Greece
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
Mount Sinai Medical Center Miami Beach FL
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
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
References provided by Crossref.org
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