462 Progression-free survival 2-progression-free survival 1 in patients with primary advanced/recurrent endometrial cancer treated with dostarlimab plus chemotherapy compared with chemotherapy alone in the ENGOT-EN6-NSGO/GOG-3031/RUBY trial

Introduction/Background

In the phase 3 RUBY trial (NCT03981796) of patients with primary advanced or recurrent endometrial cancer (pA/rEC), dostarlimab+carboplatin-paclitaxel significantly improved progression-free survival (PFS) versus carboplatin-paclitaxel alone in the mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) and overall populations with a statistically significant and clinically meaningful benefit in the overall population. Here we report on PFS2-PFS1 (defined as time from disease progression to the date of progression on the first subsequent anticancer therapy following study treatment or death by any cause) in the RUBY trial.

Methodology

>Patients with pA/rEC were randomised 1:1 to dostarlimab+carboplatin-paclitaxel or placebo+carboplatin-paclitaxel Q3W (6 cycles) followed by dostarlimab or placebo monotherapy Q6W ≤3 years or disease progression. PFS2-PFS1 was a post hoc analysis in all populations.

Results

Of 494 patients randomized (245 dostarlimab+carboplatin-paclitaxel; 249 placebo+carboplatin-paclitaxel), 118 were dMMR/MSI-H (53 dostarlimab+carboplatin-paclitaxel; 65 placebo+carboplatin-paclitaxel). In the dMMR/MSI-H population, median PFS2-PFS1 was longer in the dostarlimab+carboplatin-paclitaxel arm (17.7 vs 10.5 months; HR, 0.77; figure 1). In the mismatch repair proficient/microsatellite stable (MMRp/MSS) population, median PFS2-PFS1 was numerically higher (7.9 vs 7.1 months; HR, 0.82) favouring dostarlimab+carboplatin-paclitaxel; notably, the survival curves progressively separate after approximately 3 months and remain separated. Median PFS2-PFS1 in the overall population was also numerically higher with dostarlimab+carboplatin-paclitaxel (7.9 vs 7.3 months; HR, 0.82).

Conclusion

In the RUBY trial of patients with pA/rEC, longer PFS2-PFS1 in the dMMR/MSI-H population suggests that patients continue to derive benefit from dostarlimab treatment following disease progression. In the MMRp/MSS population, the early and progressive separation of the KM curves suggest that the PFS1 benefit of immunotherapy+carboplatin-paclitaxel may translate into better long-term outcomes, including PFS2 and eventually overall survival. Overall, these results suggest that the sequencing of dostarlimab+carboplatin-paclitaxel as 1L treatment provides benefit beyond PFS1 into PFS2. This provides further support for dostarlimab+carboplatin-paclitaxel as standard-of-care in pA/rEC.

Disclosures

This study (NCT03981796) was sponsored by GSK, Waltham, MA, USA. Third-party medical writing support: Writing and editorial support, funded and coordinated by GSK (Waltham, MA, USA), was provided by Shannon Morgan-Pelosi, PhD, and Jennifer Robertson, PhD, of Ashfield MedComms, an Inizio company. COI: Dr McCourt reports personal royalties <$200 annually from UpToDate; and personal honoraria of $200 from the Washington University OB/Gyn annual symposium. Dr Shahin reports institutional grants from AstraZeneca, GSK, and Merck; honoraria from AstraZeneca, GSK, Merck, and Seagen; expert testimony fees from Robindon & Havens PSC, Lexington KY; advisory board fees from Seagen; and board member for Unite for Her. Dr Kristeleit reports Grants from Clovis and MSD; honoraria and consultancy fees from Basilea Pharmaceutica, MSD, AstraZeneca, Clovis, Eisai, Incyte, and Pharmamar; and personal fees from GSK. Dr Willmott reports speakers' bureau fees from Astra Zeneca, Eisai, Immunogen, Merck, and Seagen, and advisory board fees from AstraZeneca, Immunogen, and Seagen. Dr Barlin reports participation on the FLORA and XPORT steering committees, participation in advisory boards for AstraZeneca, Clovis, Mersana, OncoC4, and Immunogen, and participation in speaker's bureaus for AstraZeneca and Merck. Dr Gilbert reports institutional grants from Alkermes, AstraZeneca, Clovis, Esperas, ImmunoGen Inc, IMV, Karyopharm, Merck Sharp & Dohme, Mersana, Novocure GmbH, OncoQuest Pharmaceuticals, Pfizer, Roche, and Tesaro; consulting fees from Merck; and honoraria from Alkermes, AstraZeneca, Eisai, Eisai-Merck, and GSK. Dr Cloven reports participation in advisory boards for GSK, Kartos, Novita, Takeda, Toray, Umoja, and Zentalis. Dr Bjørge reports grants/research support from AstraZeneca, honoraria/consulting fees from Onsanger, and participation in a company-sponsored speakers' bureau for MSD. Dr Black reports institutional grant fees from GSK; fees for being a member of GOG Partners Investigational Council; and medical director/owner of Trials365, LLC. Dr Mathews reports institutional research funding from AvengeBio Astellas Pharma, AstraZeneca, Deciphera, EMD Serono, Genentech, Genmab, GSK, Merck, Moderna, The National Cancer Institute, Regeneron, Seagen, and Syros. Dr Powell reports grants/research support from GSK and honoraria/consultation fees from AstraZeneca, Clovis Oncology, Eisai, GSK, Immunogen, and Merck. Dr Gilbert reports institutional grants from Alkermes, GSK, Immunogen Inc, Karyopharm, Merck Sharp & Dohme, Pfizer, Roche, and Tesaro and honoraria/consultation fees from Alkermes, Eisai, Eisai-Merck, GSK, Merck, and Novocure. Dr Mirza reports institutional research grants from Allarity, Apexigen, AstraZeneca, Boehringer Ingelheim, Clovis, GSK, Novartis, and Ultimovacs; trial chair for Deciphera, Mersana, and NuvationBio; invited speaker for AstraZeneca, GenMab, GSK, Mersana, Seagen, and Takeda; a member of board of directors and holds stocks and shares for Karyopharm and Sera Prognostics. Drs Gold, Landrum, Ronzino, Sharma, Wymenga, and Zub have nothing disclose. Drs Antony and Stevens are employees of GSK.