PFS2 and adjustment of overall survival (OS) for subsequent anticancer therapy in patients (pts) with primary advanced or recurrent endometrial cancer (pA/rEC) treated with dostarlimab plus chemotherapy or chemotherapy alone in the ENGOT-EN3-NSGO/GOG-3031/RUBY trial

Background: The RUBY trial (NCT03981796) evaluated the efficacy and safety of dostarlimab (D)+carboplatin‐paclitaxel (CP) vs CP alone in pA/rEC. D+CP significantly improved progression‐free survival (PFS) in the mismatch repair deficient/microsatellite instability‐high (dMMR/MSI‐H; HR, 0.28) and overall population (HR, 0.64) with a favorable OS trend (HR, 0.64). Here, PFS2 and OS adjusted for subsequent anticancer therapy are reported. Methods: Pts were randomised 1:1 to receive D+CP or placebo (PBO)+CP Q3W for 6 cycles, followed by D or PBO monotherapy Q6W for up to 3 years. PFS2 was a secondary endpoint for the dMMR/MSI‐H and overall populations. Post hoc treatment switching‐adjustment (for subsequent use of dostarlimab, pembrolizumab, durvalumab, nivolumab, or pembrolizumab with lenvatinib) was implemented using 2 methods: inverse probability of censoring weighting (IPCW) and rank‐preserving structural failure time (RPSFT). Results: Of 494 pts randomised (D+CP, n=245; PBO+CP, n=249), 118 were dMMR/MSI‐H (D+CP, n=53; PBO+CP, n=65). Overall, 15.5% of pts in the D+CP arm and 34.5% of pts in the PBO+CP arm received subsequent immunotherapy. PFS2 benefit was observed with D+CP for all populations (Table). When adjusted for subsequent therapy, the HRs for OS for D+CP vs PBO+CP for both IPCW and RPSFT were similar to the unadjusted HR for OS in all populations, with increased survival with D+CP (Table). Safety was reported previously. Conclusions: Consistent with results of the primary efficacy analysis, dostarlimab+CP demonstrates PFS2 and OS benefits vs PBO+CP in pts with pA/rEC despite the use of subsequent therapies. These results provide additional support for the use of dostarlimab+CP as standard of care in pts with pA/rEC. [Formula presented]. Clinical trial identification: NCT01847274. Editorial acknowledgement: Writing and editorial support, funded and coordinated by GSK, was provided by Shannon Morgan‐Pelosi, PhD, and Mary C. Wiggin, of Ashfield MedComms, an Inizio company. Legal entity responsible for the study: GSK. Funding: GSK. Disclosure: B.M. Slomovitz: Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis, Eisai, GSK, Genentech, Merck, Immunogen, Novocure; Financial Interests, Personal, Other, consultant: GOG Foundation; Non‐Financial Interests, Member of Board of Directors: GOG Foundation. N. Raaschou‐Jensen: Financial Interests, Personal, Advisory Board: Eisai. R.L. Coleman: Financial Interests, Personal, Advisory Board: AstraZeneca, agenus, Alkermes, Immunogen, Roche/Genentech, GSK, Genmab/Seagen, Epsilogen, Myriad Genetics; Financial Interests, Personal, Invited Speaker: AstraZeneca, Genmab/Seagen; Non‐Financial Interests, Principal Investigator: abbvie, immunogen, Roche/Genentech, Merck, Genmab, Clovis; Non‐Financial Interests, Project Lead, MyLung Consortium: US Oncology Research. L. Gilbert: Financial Interests, Institutional, Funding: Alkermes, AstraZeneca, Clovis, Esperas, IMV, ImmunoGen Inc, Karyopharm, Merck Sharp & Dohme, Mersana, Novocure GmbH, OncoQuest Pharmaceuticals, Pfizer, Roche, Tesaro; Financial Interests, Personal, Speaker, Consultant, Advisor: Merck, Alkermes, AstraZeneca, Eisai, Eisai‐Merck, GSK. M.A. Powell: Financial Interests, Personal, Speaker, Consultant, Advisor: GSK, Tesaro, Merck, Eisai, Seagen, Clovis Oncology, AstraZeneca. D. Cibula: Financial Interests, Personal, Advisory Board: Roche, SOTIO, Novocure, MSD, GSK, Akesobio, Seagen; Financial Interests, Personal, Invited Speaker: AstraZeneca. S. Ghamande: Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Advisory Board, also invited speaker: GSK; Financial Interests, Institutional, Coordinating PI, Clinical trial payments: GSK, Jounce; Financial Interests, Institutional, Coordinating PI, Clinical trial payment: Merck, Eisai; Financial Interests, Institutional, Coordinating PI, clinical trial payments: Mersana, AstraZeneca; Non‐Financial Interests, Advisory Role: GOG foundation. B. Ataseven: Financial Interests, Personal, Speaker, Consultant, Advisor, also support for attending meetings: AstraZeneca, GSK, Roche; Financial Interests, Personal, Speaker, Consultant, Advisor: Eisai, MSD, Novartis; Financial Interests, Personal, Advisory Board: Sanofi Aventis. D. Black: Financial Interests, Institutional, Funding: GSK; Financial Interests, Personal, Member of Board of Directors: GOG Partners Investigational Council; Financial Interests, Personal, Other: Trials365, LLC. L.J. Willmott: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Eisai, Immunogen, Merck, Seagen; Financial Interests, Personal, Advisory Board: AstraZeneca, Immunogen, Seagen. C. McCourt: Financial Interests, Personal, Royalties: UpToDate; Financial Interests, Personal, Speaker, Consultant, Advisor: Washington University. O. Doehring, J. Garside: Financial Interests, Personal, Full or part‐time Employment: GSK. T.J. Herzog: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Caris, Clovis, Eisai, Epsilogen, Genentech, GSK, Immunogen, Johnson & Johnson, Merck, Mersana, Seagen. M.R. Mirza: Financial Interests, Personal, Advisory Board: AstraZeneca, GSK, Karyopharm, Merck, Roche, Zailab; Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK; Financial Interests, Personal, Member of Board of Directors: Karyopharm; Financial Interests, Personal, Stocks/Shares: Karyopharm; Financial Interests, Institutional, Research Grant: GSK, AstraZeneca, Ultimovacs, Apexigen; Financial Interests, Institutional, Trial Chair: Deciphera; Non‐Financial Interests, Advisory Role: Ultimovacs, Apexigen. All other authors have declared no conflicts of interest.