KEY TAKEAWAYS
- The RUBY phase 3 trial aimed to investigate OS with D plus chemotherapy vs. placebo plus chemotherapy in pA/rEC.
- The dual primary endpoint was to determine OS and the secondary endpoint was safety.
- Researchers noted significant OS benefits with D plus chemotherapy in pA/rEC, supporting its use as 1L standard care.
At interim analysis (IA) 1 of Part 1 of the RUBY trial (NCT03981796), statistically significant benefit in PFS was observed with dostarlimab+carboplatin-paclitaxel (D+CP) vs placebo (PBO)+CP in the overall and mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) populations of patients with primary advanced or recurrent endometrial cancer (pA/rEC).
Matthew A. Powell and the team aimed to assess the overall survival outcomes of D plus chemotherapy compared to PBO plus chemotherapy in pA/rEC.
Researchers performed an inclusive analysis where patients with pA/rEC were randomized 1:1 to receive D+CP or PBO+CP, followed by dostarlimab or PBO for up to 3 years or until disease progression. Overall survival (OS) served as a dual-primary endpoint in the overall population and was assessed as a prespecified exploratory analysis in the dMMR/MSI-H and mismatch repair proficient/microsatellite stable (MMRp/MSS) populations. OS by molecular subgroup was evaluated as a post-hoc analysis. Safety outcomes were secondary endpoints.
At IA 2, 494 patients were randomized (245 D+CP; 249 PBO+CP). In the overall population, there was a significant 31% reduction in the risk of death with D+CP compared to PBO+CP, and a clinically meaningful improvement of 16.4 months in median OS . In the dMMR/MSI-H population, the hazard ratio (HR) for OS favored D+CP at 0.32; median OS was not reached for D+CP and 31.4 months for PBO+CP.
Among the MMRp/MSS population, the HR for OS was 0.79; median OS was 34.0 months for D+CP and 27.0 months for PBO+CP. At IA2, among 400 patients with whole exome sequencing data available, a trend towards clinical benefit with D+CP was observed across dMMR/MSI-H, TP53 mutated, and no specific molecular profile subgroups.
The study concluded that D+CP provided significant and clinically relevant overall survival benefit in the overall population compared to CP alone. A notable survival difference was observed in the dMMR/MSI-H subgroup. In MMRp/MSS patients, D+CP extended median OS by 7 months with a 21% risk reduction for death. Consistency in OS outcomes across molecular subgroups at IA2 mirrored IA1 findings. RUBY stands alone in demonstrating a statistically significant OS benefit in patients with pA/rEC, supporting dostarlimab+CP as first-line standard of care.
The study was sponsored by the Tesaro, Inc.
Source: https://cslide.ctimeetingtech.com/gynae24hybrid/attendee/confcal/show/session/10
Clinical Trial: https://clinicaltrials.gov/study/NCT03981796
Powell M .A., Auranen A, Willmott L.J, et al. (2024). “Dostarlimab plus chemotherapy in primary advanced or recurrent endometrial cancer (pA/rEC) in the RUBY trial: Overall survival (OS) by MMR status and molecular subgroups.” Presented at ESMO-GC 2024 (Abstract 37MO).
