Four-year survival outcomes with dostarlimab plus chemotherapy in mismatch repair deficient/microsatellite instability-high primary advanced or recurrent endometrial cancer in the RUBY trial

Abstract Objective Dostarlimab+carboplatin-paclitaxel (CP) demonstrated significant improvement in progression-free survival (PFS) and clinically meaningful improvement in overall survival (OS) vs CP alone among patients with dMMR/MSI-H primary advanced/recurrent endometrial cancer (EC) in Part 1 of the randomized phase 3 RUBY trial (NCT03981796). We report updated efficacy and safety data with approximately 4 years of follow-up. Methods Patients were randomized 1:1 to receive dostarlimab+CP or placebo+CP followed by dostarlimab or placebo up to 3 years or until disease progression. Descriptive analyses of OS and PFS were conducted in the dMMR/MSI-H population (median follow-up, 55.6 months). Post hoc conditional survival analyses and a mixture cure model (MCM) fitted to PFS data to estimate the proportion of patients who had curative potential are presented to provide prognostic insights into long-term survival. Results Dostarlimab+CP demonstrated sustained OS and PFS benefits. Median PFS and OS were not reached with a 66% reduction in risk of death vs placebo+CP. PFS curve plateauing (only 4 progression events with additional 2.5 years follow-up since the previous PFS analysis at interim analysis 1) demonstrated durable disease control. Patients alive at the 1- and 2-year landmarks had >80% probability of remaining alive an additional 3 and 2 years, respectively. At 4 years, the MCM analysis estimated a cure rate with dostarlimab of 54% (95% CI 35%–72%). No new safety signals were observed. Conclusions At 4 years, RUBY demonstrated sustained remission and long-term survival benefit, suggesting the potential for curative intent with dostarlimab+CP in patients with dMMR/MSI-H primary advanced or recurrent EC.