Abstract
Background: In Part 1 of the phase 3 RUBY trial (NCT0-3981796), dostarlimab+carboplatin-paclitaxel (CP) demonstrated statistically significant and clinically meaningful improvements in progression- free (PFS) and overall survival (OS) compared with CP alone among patients with primary advanced or recurrent endometrial cancer (pA/R EC). Here, we report updated efficacy and safety data with 4 years of follow-up in patients with mismatch repair-deficient/microsatellite instability-high (dMMR/ MSI-H) pA/R EC. In addition, complementary conditional survival analyses (cOS/cPFS) are presented to provide clinically relevant, prognostic insights into long-term survival potential for patient counseling. Objectives: Describe long-term progression-free survival and overall survival in patients with mismatch repair-deficient/microsatellite instability-high primary advanced or recurrent endometrial cancer in Part 1 of the RUBY trial. Describe the probability of long-term survival using conditional overall survival, a tool that may aid clinicians in counseling patients on their likelihood of long-term survival in the era of immunotherapy in endometrial cancer. Methods: Patients were randomized 1:1 to receive dostarlimab+ CP (n=53) or placebo+CP (n=65) every 3 weeks every 3 weeks (Q3W) (6 cycles) followed by dostarlimab or placebo monotherapy Q6W for up to 3 years or until disease progression. At median follow-up of 55.6 months, descriptive analyses of OS and PFS and post-hoc analyses of cOS and cPFS were conducted in the dMMR/MSI-H pA/R EC population. Results: Dostarlimab+CP demonstrated sustained OS (hazard ratio (HR), 0.34) and PFS (HR, 0.30) benefits at the 4-year analysis versus (vs) placebo+CP; only 4 additional progression events occurred during 2.5 years of additional follow-up since the first interim analysis. Four-year PFS rates of 57.9% vs 15.7% were consistent with reported 2-year PFS rates of 61.4% vs 15.7% for dostarlimab+CP vs placebo+ CP, respectively. Median OS was not reached (NR) at 4 years for dostarlimab+CP arm vs 32.8 months for placebo+CP; dostarlimab+CP resulted in a 4-year OS rate of 72.8% vs 40.3% for placebo+CP. Median duration of response (DOR) was NR for dostarlimab+CP and 4.8mo for placebo+CP; 4-year DOR rate was 54.8% for dostarlimab+ CP and 10.6% for placebo+CP. cOS analyses revealed the probability of remaining alive for an additional year increased with each subsequent year of survival. Patients alive and progression-free at 1-year had an almost 97% probability of remaining progression-free at 3 years (additional 2 years). Similar trends were observed at 2-year and 3-year cOS and at 2-year cPFS. No new safety signals were observed with additional follow-up. Conclusions: Substantial and unprecedented long-term survival benefits were demonstrated with dostarlimab+CP vs placebo+CP in patients with dMMR/MSI-H pA/R EC at 4 years. Dostarlimab+CP remains the only combination of immunotherapy and chemotherapy to demonstrate statistically significant and clinically meaningful OS benefits. Conditional survival estimates indicated that nearly all patients who remained alive and progression-free with dostarlimab+CP at 1 year remained so at 3 years, providing a powerful tool for patient counseling. Together, these data reinforce the use of dostarlimab+CP as standard-of-care and offer the potential for curative intent for patients with pA/R dMMR/MSI-H EC. Funding: GSK. Prior Presentations: Presented at the Society of Gynecological Oncology (SGO) Annual Meeting on Women’s Cancer 2026, April 10–13, San Jaun, Puerto Rico.