Quality-adjusted time without symptoms of disease progression or toxicity of treatment in patients with primary advanced or recurrent endometrial cancer treated with dostarlimab plus carboplatin-paclitaxel versus carboplatin-paclitaxel
- PMID: 40616865
- DOI: 10.1016/j.ijgc.2025.101935
Quality-adjusted time without symptoms of disease progression or toxicity of treatment in patients with primary advanced or recurrent endometrial cancer treated with dostarlimab plus carboplatin-paclitaxel versus carboplatin-paclitaxel
Abstract
Objective: In part 1 of the phase 3 RUBY trial (NCT03981796) in patients with primary advanced or recurrent endometrial cancer, dostarlimab plus carboplatin-paclitaxel significantly improved progression-free and overall survival vs placebo plus carboplatin-paclitaxel. Post hoc analyses examined the impact of adding dostarlimab to chemotherapy, compared with placebo plus chemotherapy, on quality-adjusted time without symptoms of disease progression or toxicity of treatment in this patient population.
Methods: Patients were randomized 1:1 to receive dostarlimab/placebo plus chemotherapy every 3 weeks for 6 cycles, followed by dostarlimab/placebo monotherapy every 6 weeks for up to 3 years. Data from the first interim analysis (September 28, 2022) were used, and quality of life (QoL) was assessed with the EuroQoL 5-Dimensions 5-Level questionnaire. Quality-adjusted time without symptoms of disease progression or toxicity of treatment was calculated as the sum product of the restricted mean survival times spent in 3 mutually exclusive states: toxicity, time without symptoms of disease progression or treatment toxicity, and relapse, and utilized each state's corresponding QoL.
Results: In the dostarlimab and placebo arms, 241 and 246 patients were analyzed for safety, respectively. In the overall population, the mean (95% CI) duration of quality-adjusted time without symptoms of disease progression or toxicity of treatment was significantly longer in the dostarlimab arm (24.75 months [22.88 to 26.65 months]) than in the placebo arm (20.34 months [18.95 to 21.76 months]; the mean difference [95% CI] of 4.41 months [2.01 to 6.77 months], p < .001). Benefits in quality-adjusted time without symptoms of disease progression or toxicity of treatment after dostarlimab treatment were observed regardless of mismatch repair/microsatellite instability status or toxicity criteria used and were predominantly driven by the time without symptoms of disease.
Conclusions: Dostarlimab plus carboplatin-paclitaxel treatment is associated with meaningful improvement in survival, avoidance of substantial toxicity, and maintenance of patient-reported QoL in patients with primary advanced or recurrent endometrial cancer.
Keywords: Endometrial Cancer; Health Related Quality of Life; Patient-Reported Outcomes.
Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of Competing Interests D.M.C. reports consultant fees from AstraZeneca and GSK and honoraria from AstraZeneca, GSK, ImmunoGen/AbbVie, MSD, and Pfizer. E.M.M. reports advisory board fees from AstraZeneca, GSK, and Tempus; honoraria from OncLive and Opinions in Gyn Malignancies; and support for attending meetings from Opinions in Gyn Malignancies and OncLive. L.G. reports institutional grants from Alkermes, Ascendis Pharma, AstraZeneca, Corcept Therapeutics, Daiichi Sankyo, Espersas, GOG Foundation, GSK, ImmunoGen, IMV Technologies, K-Group Beta/Zentalis Pharmaceuticals, Mersana Therapeutics, MSD, MSK Pharmalogistic, Novocure, OncoQuest Pharmaceuticals, Pfizer, Roche, Shattuck Labs, Sutro Biopharma, Tesaro/GSK, and Seagen/Pfizer; consulting fees from MSD, GSK, and Repare Therapeutics; honoraria from GSK; travel support from GOG Foundation, GSK, MSD, and Zentalis Pharmaceuticals; and participation in advisory board meetings for CanariaBio, Corcept Therapeutics, Eisai, GSK, ImmunoGen/AbbVie, Kora Healthcare, and MSD. C.M. reports institutional research funding from AADI, Artios, Astellas Pharma, AstraZeneca, Avenge Bio, Deciphera, Elucida, EMD Serono, Genentech, Genmab, GSK, Merck, Moderna, The National Cancer Institute, Regeneron, Repare, Seagen, Syros, Volastra, and Zentalis Pharmaceuticals. M.G.-M. reports support for attending meetings and/or travel from GSK. M.A.P. reports consulting fees from AstraZeneca, Clovis Oncology, Eisai, GSK/Tesaro, MSD, and Seagen/Pfizer. A.K.L.R. reports institutional grants from Cogent Biosciences, Deciphera, Dutch Cancer Society, Genmab, GSK/Tesaro, MSD, and Regeneron; payments to the institution for lectures on palliative care and expensive drugs; and a leadership role for cieBOM. N.G.C. reports advisory board fees for AbbVie, Genmab, GSK, ImmunoGen/AbbVie, Kartos Therapeutics, Novita Pharmaceuticals, and Zentalis Pharmaceuticals. G.E. reports consulting fees from MSD; payment or honoraria from Eisai; travel support from MSD; and participation on a data safety monitoring board or advisory board from Eisai, GSK, and Regeneron. B.M.-M. reports honoraria from AstraZeneca, GSK, and HealthQuest; advisory board fees from GSK and Seagen/Pfizer; and support for clinical trials from AstraZeneca AB, AstraZeneca Pharma, Clovis Oncology, Karthos Therapeutics, MSD, Mersana Therapeutics, MSD Polska Sp zoo, Seagen/Pfizer, Parexel International Limited; Poland sp zoo, Regeneron, Roche Polska sp zoo, Tesaro/GSK, and Quiniles Eastern Holdings. B.P. reports institutional research support from Acrivon Therapeutics, Agenus, Alkermes, AstraZeneca, Celgene/Bristol Myers Squibb, Clovis Oncology, Daiichi Sankyo, DualityBio, Eisai, I-Mab Biopharma, ImmunoGen/AbbVie, Imunon, Incyte, Karyopharm Therapeutics, LOXO Oncology/Lilly, Mersana Therapeutics, MSD, NRG Oncology, Onconova Therapeutics/Traws Pharma, Pfizer, Roche/Genentech, Seagen/Pfizer, Sutro Biopharma, Takeda, Tesaro/GSK, Toray Industries, VBL Therapeutics, and Xencor; consulting fees from AstraZeneca, BioNTech, DualityBio, Eisai, GOG Foundation, ImmunoGen/AbbVie, Imunon, Imvax, Incyte, InxMed, Karyopharm Therapeutics, Mersana Therapeutics, Natera, Onconova Therapeutics/Traws Pharma, OnCusp Therapeutics, R Pharm, Regeneron, Seagen/Pfizer, Sutro Biopharma, and Tesaro/GSK; honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from Albert Einstein-Montefiore, Aptitude Health, Bio Ascend, Colorado University, Curio, Lankenau Medical Center, OncLive, PeerView, PERS, Vanium Group, and Yale University; travel support from GOG Partners; participation on a data safety monitoring or advisory board for AstraZeneca, BeiGene, BioNTech, Daiichi Sankyo, GOG Foundation, I-Mab Biopharma, Imunon, ImmunoGen/AbbVie, Imvax, InxMed, LOXO Oncology/Lilly, Mersana Therapeutics, MSD, Nuvation Bio, Onconova Therapeutics/Traws Pharma, Sutro Biopharma, Tesaro/GSK, and Toray Industries; and membership on the GOG Partners Leadership committee, vice presidency of the NYOB Society, and membership on the SGO board of directors. V.S. reports consultation and advisory boards for AstraZeneca, Eisai, GSK, and MSD. S.B. reports consulting fees from ImmunoGen/AbbVie. P.B. reports being a member of a steering committee for GSK. F.J.B. reports institutional research grants from AstraZeneca, Clovis Oncology, Eisai, ImmunoGen/AbbVie, MSD, Natera, and Tempus; royalty fees from UpToDate; advisory board fees from AstraZeneca, BioNTech, Clovis Oncology, Daiichi Sankyo, Eisai, EMD Serono, GSK, ImmunoGen/AbbVie, MSD, and Myriad Genetics; CME lecture fees from Clinical Care Options, Clinical Educational Concepts, CMR institute, Global Learning Initiative/Prova, GOG Foundation, i3Health, Medscape/WebMD, Med Learning, OncLive, Research To Practice, and Targeted Oncology; travel support from BioNTech and GSK; and leadership roles in IGCS Education360 (co-chair), NRG Oncology developmental therapeutics committee (co-chair), and SGO (board member). O.A., G.A., and J.G. are employed by GSK and hold financial equity in GSK. M.R.M. reports advisory board fees from AbbVie, Allarity Therapeutics, AstraZeneca, BIOCAD, BioNTech, Daiichi Sankyo, Eisai, Genmab, GSK, ImmunoGen/AbbVie, Incyte, Karyopharm Therapeutics, MSD, Regeneron, and Zai Lab; honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from AstraZeneca, Eisai, GSK, Takeda, and Zai Lab; support for meetings or travel from AstraZeneca and GSK; board of director roles at Karyopharm Therapeutics and Sera Prognostics; and stock options from Karyopharm Therapeutics and Sera Prognostics. The remaining authors have nothing to disclose.