Background
RUBY (ENGOT-EN6/GOG-3031) was a phase III double-blind, placebo-controlled trial evaluating dostarlimab (anti-PD-1) plus carboplatin-paclitaxel as first-line treatment of primary advanced (stage III/IV) or first recurrent endometrial cancer. Published simultaneously with NRG-GY018 (pembrolizumab) in NEJM April 2023, RUBY tested a parallel anti-PD-1 approach with prospective MMR stratification and long-term maintenance.
Interventions and follow up
Arm A: Carboplatin AUC 5 + paclitaxel 175 mg/m² q21d × 6 cycles + placebo q3w → placebo maintenance q6w up to 3 years
Arm B: Carboplatin AUC 5 + paclitaxel 175 mg/m² q21d × 6 cycles + dostarlimab 500 mg q3w → dostarlimab maintenance 1000 mg q6w up to 3 years
Primary endpoint: PFS (in dMMR and ITT populations)
mFollow-up: 24.8 months
Arm B: Carboplatin AUC 5 + paclitaxel 175 mg/m² q21d × 6 cycles + dostarlimab 500 mg q3w → dostarlimab maintenance 1000 mg q6w up to 3 years
Primary endpoint: PFS (in dMMR and ITT populations)
mFollow-up: 24.8 months
Results
dMMR 24-mo PFS: 61.4% (95% CI 46.3–73.4) vs 15.7% (7.2–27.0); HR 0.28, P<.001
All patients mPFS: 11.8 vs 7.9 months (HR 0.64, 95% CI 0.51–0.80, P<.001)
OS: immature at primary analysis; OS update (Ann Oncol 2024) showed significant OS benefit in dMMR (HR 0.30)
All patients mPFS: 11.8 vs 7.9 months (HR 0.64, 95% CI 0.51–0.80, P<.001)
OS: immature at primary analysis; OS update (Ann Oncol 2024) showed significant OS benefit in dMMR (HR 0.30)
Adverse events
Overall: Grade ≥3 AEs broadly consistent with carboplatin-paclitaxel and the known dostarlimab profile; discontinuation due to AEs 12% vs 4%
Immune-mediated: hypothyroidism (22% any grade), AST increase, colitis; Grade ≥3 immune AEs ~10%
Immune-mediated: hypothyroidism (22% any grade), AST increase, colitis; Grade ≥3 immune AEs ~10%
Conclusions
Dostarlimab plus carboplatin-paclitaxel significantly improved PFS in both dMMR and all-comers with advanced or recurrent endometrial cancer, with a dramatic benefit in dMMR tumors (24-mo PFS 61.4% vs 15.7%), establishing anti-PD-1 + chemotherapy as a new standard of care alongside pembrolizumab-based regimens.
Key Limitations
OS data immature at primary NEJM publication (subsequently updated); dMMR cohort only 23.9% of enrolled population; PFS in pMMR/all population (HR 0.64) consistent with NRG-GY018; no head-to-head between dostarlimab (PD-1) and pembrolizumab (PD-1); 3-year maintenance duration vs NRG-GY018's ~14 cycles complicates cross-trial comparison; RUBY enrolled primary advanced including stage III patients not required to have measurable disease (vs NRG-GY018 requiring measurable or stage IVB).
Clinical Context
RUBY and NRG-GY018 were simultaneously published in NEJM April 2023 and together transformed first-line endometrial cancer treatment. FDA approved dostarlimab + carbo/pac for primary advanced or recurrent endometrial cancer in 2023 (full approval for all-comers August 2023). RUBY's survival update (Ann Oncol 2024, PMID 38866180) showed a significant OS benefit in dMMR patients (HR 0.30); the OS benefit in pMMR remains under evaluation. RUBY and NRG-GY018 collectively establish IO-containing chemotherapy as standard of care regardless of MMR status.