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Abstract
Introduction/Background In the phase 3 RUBY trial (NCT03981796) in patients with primary advanced or recurrent endometrial cancer (pA/rEC), dostarlimab+carboplatin-paclitaxel (CP) significantly improved progression-free survival (PFS) versus CP in the mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) and overall populations and overall survival (OS) in the overall population. Treatments in pA/rEC aim to improve PFS and OS while maintaining health-related quality of life (HRQoL). By assessing time to deterioration (TTD), the length of HRQoL maintenance can be compared between trial arms.
Methodology Patients with pA/rEC were randomised 1:1 to receive dostarlimab+CP or placebo+CP Q3W for 6 cycles, followed by dostarlimab or placebo monotherapy Q6W for ≤3 years. Post-hoc TTD analyses were conducted for EORTC Quality of Life Questionnaire Core 30 (QLQ-C30) and Endometrial Cancer 24 (QLQ-EN24). Time to first deterioration (TTD1) was first deterioration of ≥10 points versus baseline. Time to permanent deterioration (TTDP) was deterioration of ≥10 points versus baseline that was sustained at all subsequent time points.
Results Of 494 patients randomised, 118 were dMMR/MSI-H (53 dostarlimab+CP; 65 placebo+CP). In the dMMR/MSI-H population, most QLQ-C30 domains directionally favored dostarlimab+CP for TTD1 and TTDP; social and role functioning were longer for TTD1; global QoL and role functioning showed delayed TTDP (figure 1). Gastrointestinal was the only QLQ-EN24 domain with an observed difference in this population (TTDP only) in the dostarlimab+CP arm. In the overall population, neither QLQ-C30 nor QLQ-EN24 showed differences between arms for TTD1 or TTDP.
Analysis of EORTC QLQ-c30 and EORTC QLQ-EN24 (A)TTD1 and (B) TTDP in the dMMR/MSI-H population
Conclusion Dostarlimab+CP demonstrated clinically meaningful delay in TTDP for QoL in the dMMR/MSI-H population compared to CP in addition to lengthening of TTD1 and delayed TTDP in several QLQ-C30 and QLQ-EN24 domains; no detriment was observed in the overall population. These findings, together with PFS and OS benefits, further support the use of dostarlimab+CP as a standard of care in patients with dMMR/MSI-H pA/rEC.
Disclosures Disclosures: This study was funded by GSK (Waltham, MA, USA).
Clinical trial registration number: NCT03981796
Topic area: Endometrial cancer
COI: Dr Boere reports institutional research grant from GSK; and institutional advisory board meeting fees from AstraZeneca and GSK.
Dr Pothuri reports institutional grant support from AstraZeneca, Celsion, Clovis Oncology, Eisai, Genentech/Roche, Karyopharm, Merck, Mersana, SeaGen, Sutro Biopharma, Takeda Pharmaceuticals, Tesaro/GSK, Toray, VBL Therapeutics; consulting fees from AstraZeneca, Atossa, Clovis Oncology, Deciphera, Elevar Therapeutics, Imab, Merck, Mersana, Sutro Biopharma, Tesaro/GSK, and Toray; support for attending meetings from GOG Foundation; advisory board fees from Arquer Diagnostics, AstraZeneca, Atossa, Clovis Oncology, Deciphera, Eisai, Elevar Therapeutics, GOG Foundation, Imab, Lilly, Merck, Mersana, Seagen, Sutro Biopharma, Tesaro/GSK, Toray, VBL Therapeutics; and non-compensated leadership fees from NYOB Society Secretary, SGO Clinical Practice Committee Chair, and SGO COVID-19 Taskforce Co-Chair.
Dr Sukhina reports institutional grants from Tesaro
Dr Myers reports honoraria from Immunogen.
Dr Tuninetti reports institutional grants and honoraria from GSK, MMSD, and EISAI; meeting support from GSK; and paticipation on Data Safety Monitoring or Advisory Boards for GSK and MSD.
Dr Secord reports support paid to her institution from GSK for present IGCS abstract; institutional grant support from AbbVie, Aravive, Astra Zeneca, Clovis, Eisai, Ellipses, I-MAB Biopharma, Immunogen, Merck, Oncoquest/Canaria Bio, Roche/Genentech, Seagen Inc., TapImmune, Tesaro/GSK, VBL Therapeutics; honoraria from @Point of Care Clinical Care Options Curio Science, Peerview, Bio ASCEND, RTP, GOG Foundation (Highlight reel) and GOG Foundation Symposium; patent issued for ‘Blood based biomarkers in ovarian cancer;’ non-compensation for participation on a data safety monitoring board/advisory board from AstraZeneca, Clovis, Gilead, Immunogen, Imvax, Merck, Mersana, Natera, Onconova, and OncoQuest; uncompensated leadership roles with SGO, AAOGF, and NRG and compensated role from GOG; receipt of medical writing support from AstraZeneca; and uncompensated Clinical Trial Steering Committees for the AXLerate trial (Aravive), AtTEnd trial (Hoffman-LaRoche), Oval Trial (VBL Therapeutics), FLORA-5 trial (CanariaBio), and QPT-ORE-004 (CanariaBio).
Dr Heitz reports honoraria from AstraZeneca, GSK, Tesaro, and Roche; consulting fees from AstraZeneca, GSK, Tesaro and Roche.
Dr Auranen reports advisory board fees from GSK and MSD.
Dr Gilbert reports institutional grants from Alkermes, AstraZeneca, Clovis, Esperas, IMV, ImmunoGen Inc, Karyopharm, Merck Sharp & Dohme, Mersana, Novocure GmbH, OncoQuest Pharmaceuticals, Pfizer, Roche, and Tesaro; consulting fees from Merck; honoraria from Alkermes, AstraZeneca, Eisai, Eisai-Merck, and GSK.
Dr Slomovitz reports advisory fees from AstraZeneca, Clovis, Genentech, GSK, GOG Foundation, Merck, Myriad, Jazz Pharma, Onconova, Nuvation Bio, EQRX, Regeneron, Eisai, and Incyte; and Board of Directors for GOG Foundation and HOW: Hearing Ovarian Cancer Whispers.
Dr Willmott resports speaker’s bureau fees from Astra Zeneca, Eisai, Immunogen, Merck, and Seagen; and advisory board fees from AstraZeneca, Immunogen, and Seagen.
Dr Powell reports consulting fees from GSK, Tesaro, Merck, Eisai, SeaGen, Clovis Oncology, and AstraZeneca.
Dr McCourt reports persnal royalties <$200 annually from UpToDate; and personal honoraria of $200 from the Washington University OB/Gyn annual symposium.
Drs Nowicki, Nevadunsky and Gold have nothing to disclose.
Dr Mirza reports consulting fees from AstraZeneca, Biocad, GSK, Karyopharm, Merck, Roche, and Zailab; speakers’ bureau fees from AstraZeneca and GSK; research funding (to institution) from Apexigen, AstraZeneca, Deciphera (trial chair), GSK, and Ultimovacs; and personal financial interest in Karyopharm (stocks/shares, member of board of directors).
Dr Cloven reports advisory board fees for Aadii, GSK, Kartos 2022, Novita pharmaceuticals 2023, Tarveda Therapeutics, Toray, Umoja 2022, Zentalis
Ms Vincent is an employee of GSK.
Dr Simang is an employee of GSK and KLIFO GmbH (Munich, Germany)
Third-party medical writing support: Medical writing and editorial support were coordinated by GSK, and provided by Shannon Morgan-Pelosi, PhD,CMPP, and Jennifer Robertson, PhD, CMPP, of Ashfield MedComms, an Inizio company.