750P - 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. Table: 750P

^aInvestigator assessment per RECIST v1.1 ^bD+CP increases survival by AF

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.