Dostarlimab plus chemotherapy is now approved for all adults with primary advanced or recurrent endometrial cancer, regardless of mismatch repair or microsatellite instability status. The RUBY trial demonstrated a 31% reduction in death risk (HR 0.69) and significant progression-free survival benefit across all patient populations, making this a new standard-of-care option for first-line treatment.
Study Design & Population
- Design: Randomized, multicenter, double-blind, placebo-controlled trial (RUBY)
- Sample size: 494 patients
- Population: Primary advanced or recurrent endometrial cancer
- Stratification: MMR/MSI status, prior radiotherapy, disease status (recurrent, primary stage III/IV)
- Treatment arms: Dostarlimab vs placebo with carboplatin/paclitaxel
Key Findings
- Overall survival: 44.6 months dostarlimab vs 28.2 months placebo (HR 0.69, 95% CI 0.54-0.89, P=.002)
- Progression-free survival: 11.8 months vs 7.9 months (HR 0.64, 95% CI 0.51-0.80, P<.0001)
- dMMR/MSI-H population: 68% reduction in death risk (HR 0.32, P=.0002)
- MMRp/MSS population: 21% reduction in death risk (HR 0.79, P=.0493)
- MMRp/MSS median OS: 34.0 months vs 27.0 months chemotherapy alone
Clinical Implications
- Expands treatment options beyond biomarker-selected patients to include all endometrial cancer patients
- Establishes immunotherapy-chemotherapy combination as first-line standard across MMR/MSI status
- Provides substantial benefit even in historically immune-resistant MMRp/MSS tumors
- No new safety signals identified beyond known dostarlimab profile
Limitations
- Single trial supporting broad approval across biomarker populations
- Median follow-up duration not specified in current analysis
- MMRp/MSS benefit less dramatic than dMMR/MSI-H population
- Cost-effectiveness analysis not provided for universal use
Source: https://www.oncologynewscentral.com/article/fda-expands-dostarlimab-approval-in-endometrial-cancer
