734P - Impact of investigator-assessed response on overall survival (OS) in patients (pts) with primary advanced or recurrent endometrial cancer (pA/rEC) in the ENGOT-EN6-NSGO/GOG3031/RUBY trial

Background

In RUBY (NCT03981796), dostarlimab (D)+carboplatin-paclitaxel (CP) demonstrated significant OS benefits vs placebo (PBO)+CP in pts with pA/rEC. Differential response rates alone insufficiently describe the impact on long-term outcomes, in part because of high response rates with CP, albeit with a lack of durability. Response-based modeling may describe OS benefits associated with D+CP. This analysis investigated the impact of response on OS in the intent-to-treat population of RUBY.

Methods

In this post hoc exploratory OS analysis, surviving pts with evaluable disease were grouped by investigator-assessed objective response at 3 months (3-mo landmark). Landmarking eliminates immortal time bias. Pts with complete/partial response were classified as responders; those with stable or progressed disease were classified as nonresponders. Postlandmark OS was assessed using Kaplan-Meier methods and Cox proportional hazards models. Landmark analyses based on response at 1.5 or 4.5 mo were explored in sensitivity analyses.

Results

Overall, 196 pts in D+CP and 200 in PBO+CP were evaluable; 122 and 107, respectively, were responders; 74 and 93, respectively, were nonresponders at the 3-mo landmark. For responders, median (mo [95% CI]) postlandmark OS was not reached (NR) for D+CP (NR [NR-NR]) or PBO+CP (NR [18.5-NR]). For nonresponders, median OS was NR (21.6-NR) for D+CP and 26.8 (15.2-NR) for PBO+CP. HRs and postlandmark OS probabilities are shown in the table. Sensitivity analyses yielded similar results.

Conclusions

Outcomes associated with response to dostarlimab+CP were favorable compared with response to PBO+CP, reflecting the improved durability of benefit. OS rates suggest potential long-term benefits in responders and nonresponders. These findings provide further support for the use of D+CP as a standard of care in pts with pA/rEC. Table: 734P

Postlandmark OS rates among responders and nonresponders

Clinical trial identification

NCT03981796.

Editorial acknowledgement

Medical editorial assistance was provided by Nucleus Global, an Inizio company, and funded by GSK.

Legal entity responsible for the study

GSK.

Funding

This study was funded by GSK.

Disclosure

M.R. Mirza: Financial Interests, Personal, Advisory Role: AstraZeneca, Biocad, GSK, Karyopharm, Merck, Roche, Zailab; Financial Interests, Personal, Speaker’s Bureau, Honoraria: AstraZeneca, GSK; Financial Interests, Personal, Stocks or ownership: Karyopharm; Financial Interests, Institutional, Research Funding: Apexigen, AstraZeneca, GSK, Ultimovacs; Financial Interests, Institutional, Research Funding, Trial Chair: Deciphera ; Financial Interests, Personal, Member of Board of Directors: Karyopharm. C. Mathews: Financial Interests, Institutional, Research Funding: AvengeBio Astellas Pharma, AstraZeneca, Deciphera, EMD Serono, Genentech, Genmab, GSK, Merck, Moderna, The National Cancer Institute, Regeneron, Seagen, Syros. A. Koliadi: Financial Interests, Personal, Speaker, Consultant, Advisor: Eisai, GSK. L. Gilbert: Financial Interests, Institutional, Research Grant: Alkermes, AstraZeneca, Clovis, Corcept Therapeutics, Esperas, GOG Foundation, GSK, ImmunoGen, IMV, Karyopharm, K-Group Beta, Merck Sharp &Dohme, Mersana Therapeutics, Novocure GmbH, OncoQuest Pharmaceuticals, Roche, Shattuck Labs, Sutro BioPharma, Tesaro; Financial Interests, Personal, Speaker, Consultant, Advisor: GSK, Merck; Financial Interests, Personal, Speaker’s Bureau, Honoraria: CanariaBio, Eisai, Eisai-Merck, GOG Foundation, GSK, ImmunoGen, Kora Healthcare, Merck; Financial Interests, Personal, Financially compensated role, Support for attending meetings and/or travel: EndomEra, GOG Foundation, GSK, Merck, Zentalis; Financial Interests, Personal, Advisory Board: CanariaBio, Eisai, Eisai-Merck, GOG Foundation, GSK, ImmunoGen, Kora Healthcare, Merck. B.M. Slomovitz: Financial Interests, Personal, Speaker, Consultant, Advisor: Aadi Biosciences, AstraZeneca, BioNTech, Clovis Oncology, Eisai, Genmab, Genentech, Gilead, GSK, Incyte, Karyopharm, Merck, Novartis, Novocure, Regeneron, Seagen; Financial Interests, Personal, Speaker’s Bureau, Honoraria: Seagen. B.J. Monk: Financial Interests, Personal, Speaker, Consultant, Advisor: Agenus, Akeso Biopharma, Amgen, Aravive, Bayer, Elevar, EMD Merck, Genmab/Seagen, GOG Foundation, Gradalis, ImmunoGen, Iovance, Karyopharm, MacroGenics, Mersana, Myriad, Novartis, Novocure, Pfizer, Puma, Regeneron, Sorrento, US Oncology Research, VBL; Financial Interests, Personal, Speaker’s Bureau, Honoraria: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Clovis, Eisai, Merck, Roche/Genentech, Tesaro/GSK. P. Braly: Financial Interests, Institutional, Research Funding: GSK. D. Black: Financial Interests, Institutional, Research Grant: GSK; Financial Interests, Personal, Membership or affiliation, Membership fees: GOG Partners Investigational Council ; Financial Interests, Personal, Other, Medical Director/ Owner: Trials365, LLC. S.J. Lubinga: Financial Interests, Personal, Full or part-time Employment: GSK; Financial Interests, Personal, Stocks/Shares: GSK. D.J. Sharpe: Financial Interests, Institutional, Full or part-time Employment: Parexel International; Financial Interests, Institutional, Other, Organization received funds to conduct statistical research: Bristol Myers Squibb, GSK. M.A. Powell: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Clovis Oncology, Eisai, GSK, Merck, Seagen, Tesaro. All other authors have declared no conflicts of interest.