Overall survival in patients with endometrial cancer treated with dostarlimab plus carboplatin-paclitaxel in the randomized ENGOT-EN6/GOG-3031/RUBY trial.

Autor:	Powell MA; National Cancer Institute sponsored NRG Oncology, Washington University School of Medicine, St Louis, USA., Bjørge L; Haukeland University Hospital, Bergen; University of Bergen, Bergen, Norway., Willmott L; Arizona Oncology, Phoenix, USA., Novák Z; Department of Gynecology, Hungarian National Institute of Oncology, Budapest, Hungary., Black D; Willis-Knighton Cancer Center, Willis-Knighton Health System, Gynecologic Oncology Associates, Shreveport, USA., Gilbert L; Division of Gynecologic Oncology, McGill University Health Centre, Montreal; Gerald Bronfman Department of Oncology, McGill University, Montreal, Canada., Sharma S; Department of Obstetrics/Gynecology, AMITA Health Adventist Medical Center, Hinsdale, USA., Valabrega G; Ordine Mauriziano Torino and University of Torino, Torino, Italy., Landrum LM; Indiana University Health & Simon Cancer Center, Indianapolis, USA., Gropp-Meier M; AGO Study Group, Wiesbaden; Oberschwabenklinik, St. Elisabethen-Klinikum, Ravensburg, Germany., Stuckey A; Women and Infants Hospital of Rhode Island, Providence, USA., Boere I; Department of Medical Oncology, Erasmus MC Cancer Centre, Rotterdam, The Netherlands., Gold MA; Oklahoma Cancer Specialists and Research Institute, Tulsa, USA., Segev Y; Gynecology Oncology Division, Department of Obstetrics and Gynaecology, Carmel Medical Center, Haifa, Israel., Gill SE; St. Joseph's/Candler Gynecologic Oncology & Surgical Specialists, Candler Hospital, Savannah, USA., Gennigens C; Department of Medical Oncology, CHU of Liège, Liège; Belgium and Luxembourg Gynaecological Oncology Group (BGOG), Leuven, Belgium., Sebastianelli A; CHU de Québec-Université Laval, Quebec, Canada., Shahin MS; Hanjani Institute for Gynecologic Oncology, Abington Hospital-Jefferson Health, Asplundh Cancer Pavilion, Sidney Kimmel Medical College of Thomas Jefferson University, Willow Grove., Pothuri B; GOG Foundation; Departments of Obstetrics/Gynecology and Medicine, Division of Gynecologic Oncology, Laura & Isaac Perlmutter Cancer Center, NYU Langone Health, New York., Monk BJ; GOG Foundation; Department of Florida Cancer Specialists and Research Institute, West Palm Beach., Buscema J; Department of Arizona Oncology, Tucson., Coleman RL; Department of Texas Oncology, US Oncology Network, The Woodlands., Slomovitz BM; Department of Gynecologic Oncology, Mount Sinai Medical Center, Miami Beach; Department of Obstetrics and Gynecology, Florida International University, Miami Beach., Ring KL; University of Virginia Health System, Charlottesville., Herzog TJ; Department of Obstetrics and Gynecology, University of Cincinnati Cancer Center, University of Cincinnati, Cincinnati., Balas MM; GSK, New York, USA., Grimshaw M; GSK, London, UK., Stevens S; GSK, London, UK., Lai DW; GSK, Los Angeles., McCourt C; Division of Gynecologic Oncology, Washington University School of Medicine, Washington University in St Louis, St Louis, USA., Mirza MR; Rigshospitalet, Copenhagen University Hospital, Copenhagen; Nordic Society of Gynaecologic Oncology-Clinical Trial Unit, Copenhagen, Denmark. Electronic address: mansoor@rh.regionh.dk.
Jazyk:	angličtina
Zdroj:	Annals of oncology : official journal of the European Society for Medical Oncology [Ann Oncol] 2024 Aug; Vol. 35 (8), pp. 728-738. Date of Electronic Publication: 2024 Jun 10.
DOI:	10.1016/j.annonc.2024.05.546
Abstrakt:	Background: Part 1 of the RUBY trial (NCT03981796) evaluated dostarlimab plus carboplatin-paclitaxel compared with placebo plus carboplatin-paclitaxel in patients with primary advanced or recurrent endometrial cancer (EC). At the first interim analysis, the trial met one of its dual primary endpoints with statistically significant progression-free survival benefits in the mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) and overall populations. Overall survival (OS) results are reported from the second interim analysis. Patients and Methods: RUBY is a phase III, global, double-blind, randomized, placebo-controlled trial. Part 1 of RUBY enrolled eligible patients with primary advanced stage III or IV or first recurrent EC who were randomly assigned (1 : 1) to receive either dostarlimab (500 mg) or placebo, plus carboplatin-paclitaxel every 3 weeks for 6 cycles followed by dostarlimab (1000 mg) or placebo every 6 weeks for up to 3 years. OS was a dual primary endpoint. Results: A total of 494 patients were randomized (245 in the dostarlimab arm; 249 in the placebo arm). In the overall population, with 51% maturity, RUBY met the dual primary endpoint for OS at this second interim analysis, with a statistically significant reduction in the risk of death [hazard ratio (HR) = 0.69, 95% confidence interval (CI) 0.54-0.89, P = 0.0020] in patients treated with dostarlimab plus carboplatin-paclitaxel versus carboplatin-paclitaxel alone. The risk of death was lower in the dMMR/MSI-H population (HR = 0.32, 95% CI 0.17-0.63, nominal P = 0.0002) and a trend in favor of dostarlimab was seen in the mismatch repair-proficient/microsatellite stable population (HR = 0.79, 95% CI 0.60-1.04, nominal P = 0.0493). The safety profile for dostarlimab plus carboplatin-paclitaxel was consistent with the first interim analysis. Conclusions: Dostarlimab in combination with carboplatin-paclitaxel demonstrated a statistically significant and clinically meaningful OS benefit in the overall population of patients with primary advanced or recurrent EC while demonstrating an acceptable safety profile. (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze:	MEDLINE
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