Introduction/Background In the Phase III randomised, double-blind, multicentre RUBY study (NCT03981796), dostarlimab plus carboplatin-paclitaxel (dostarlimab+CP) resulted in significant improvement in progression-free survival versus CP alone in patients with primary advanced or recurrent endometrial cancer (AR EC). This post-hoc survival analysis explored quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) in RUBY part 1.
Methodology Patients (N=494) were randomised 1:1 to receive dostarlimab+CP or placebo + CP every 3 weeks (Q3W) ≥6 cycles, then dostarlimab or placebo Q6W ≤3 years. Q-TWiST was calculated based on the safety population (patients receiving any amount of study drug; N=486) as the sum product of mean survival time (months; restricted to study follow-up time) in three mutually exclusive states and each state’s corresponding quality of life (EQ-5D-5L). States were time without symptoms of progression or toxicity (TWiST), toxicity (time from randomisation to progression during which patients experienced Grade ≥3 adverse events), and relapse (time from progression to any-cause death).
Results Overall, median follow-up duration was 20.5 months. For mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) patients, restricted mean Q-TWiST was significantly (P<0.001*) longer in the dostarlimab+CP versus CP group (difference: 5.4 months; actual restricted mean: 22.7 versus 17.2 months, respectively). Q-TWiST was also significantly (P<0.001*) longer in the dostarlimab+CP versus CP group for MMR-proficient/microsatellite-stable (MMRp/MSS) patients (difference: 2.6 months; actual restricted mean: 22.6 vs 20.1 months, respectively) (table 1). These results demonstrate clinically important improvements in Q-TWiST for the dostarlimab+CP versus CP group in both MMRp/MSS and dMMR/MSI-H populations; mean survival gains were 2.6 and 5.4 months, respectively. Similar outcomes were observed with Grade ≥2 AEs included in toxicity definition.
Conclusion In patients with AR EC, dostarlimab+CP had significantly longer quality-adjusted survival time than CP alone, indicating that dostarlimab+CP improves survival while preserving Q-TWiST.
Funding GSK213361. Editorial support provided by Fishawack Health, funded by GSK.
Disclosures DC has received consultation and speaking fees for Astra Zeneca, Eisai, GSK, Immunogen, and Seagen/Genmab.
LB has received grants/research support from AstraZeneca, honoraria/consulting fees from Onsanger, and participation in a company sponsored speakers’ bureau for MSD.
RLC has received grants/research support from AstraZeneca, Clovis, Genelux, Genmab, Merck, Immunogen, and Roche/Genentech, consulting fees from Agenus, Alkermes, AstraZeneca, Clovis, Deciphera, Genelux, Genmab, GSK, Immunogen, OncoQuest, Onxerna, Regeneron, Roche/Genentech, Novocure, Merck, and Abbvie, honoraria from AstraZeneca, Clovis, Roche/Genentech, and Merck and participation on a Data Safety Monitoring Board or Advisory Board for VBL Therapeutics and Eisai/BMS.
OZ, SG, MGT, AR, RA and CMc have no conflicts of interest to disclose.
EM has received honoraria/consultation fees from Onc Live/Chemotherapy Foundation Symposium.
CMa has received institutional research funding from The National Cancer Institute, Syros, Deciphera, Astellas Pharma, Seagen, Genmab, EMD Serono, Merck, Regeneron, Moderna, AstraZeneca, GSK, AvengeBio and Genentech.
LCH has received honoraria/consultation fees from Amgen, AstraZeneca, Clovis Oncology, Eisai, GSK, Janssen, MSD, Novartis, Pfizer, PharmaMar, and Roche..
MP has received grants/research support from GSK and honoraria/consultation fees from GSK, Merck, Eisai, Clovis Oncology, Immunogen, and AstraZeneca.
LG has received institutional grants from Pfizer, Merck Sharp & Dohme, Karyopharm, Tesaro, Alkermes, GSK, Immunogen Inc and Roche and honoraria/consultation fees from GSK, Merck, Eisai, Eisai-Merck, Alkermes, and Novocure.
NC has participated in advisory boards for GSK, Toray, Takeda, Umoja, Kartos, Novita, and Zentalis.
BJM has received honoraria for speaking/consultation from Acrivon, Adaptimmune, Agenus, Akeso Bio, Amgen, Aravive, AstraZeneca, Bayer, Clovis, Easai, Elevar, EMD Merck, Genmab/Seagen, GOG Foundation, Gradalis, Heng Rui, Immunogen, Karyopharm, Iovance, Laekna Health Care, Merck, Mersana, Myriad, Novartis, Novocure, OncoC4, Panavance, Pieris, Pfizer, Puma, Regeneron, Roche/Genentech, Sorrento, Tesaro/GSK, US Oncology Research, VBL, Verastem, and Zentalis
BP has received grants/research support from Tesaro/GSK, Merck, AstraZeneca, Karyopharm, Sutro, Immunogen, VBL Therapeutics, Onconova,clovis, Genentech, Mersana, Ceslion, Takada, Incyte, Toray, and Seagen and honoraria/consultation fees from Tesaro/GSK, Merck, AstraZeneca, Eli Lilu, Sutro, SeaGen, Eisai, Natera, and GOG Partners.
JG and OA are employees of GSK.
MRM has received institutional research grants from Allarity, Apexigen, AstraZeneca, Boehringer Ingelheim, Clovis, GSK, Novartis, and Ultimovacs, been a trial chair for Deciphera, Mersana, and NuvationBio, been an invited speaker for AstraZeneca, GenMab, GSK, Mersana, Seagen, and Takeda, been a member of board of directors and holds stocks and shares for Karyopharm and Sera Prognostics.
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