KEY TAKEAWAYS
- The RUBY phase 3 trial aimed to assess OS in primary advanced or recurrent endometrial cancer patients receiving dostarlimab + CP.
- The primary endpoints included PFS in both dMMR/MSI-H and overall populations, and OS in the overall population.
- Dostarlimab + CP demonstrated significant OS benefit in the overall population and substantial improvement in the dMMR/MSI-H subgroup.
In the initial and interim analysis of the RUBY phase 1 trial (NCT03981796), progression-free survival (PFS) met the two primary endpoints, namely the overall population and endometrial cancer patients with mismatch repair/microsatellite instability-high (dMMR/MSI-H). The results showed statistically significant significance in the control arm, which was carboplatin-paclitaxel (CP) chemotherapy alone, and the absence of dMMR/MSI-H.
Accordingly, at an average overall survival (OS) rate of 33%, dostarlimab + CP demonstrated favorable OS, leading to approval in many countries for the treatment of dMMR/MSI-1 H pA/rEC uterine cancer patients.
Matthew A. Powell and the team conducted a study that aimed to assess PFS and OS outcomes in patients with primary advanced or recurrent endometrial cancer.
Patients with pA/rEC were randomized in a 1:1 ratio to receive either dostarlimab+carboplatin-paclitaxel or placebo (PBO) + carboplatin-paclitaxel every 3 weeks for 6 cycles, followed by dostarlimab or PBO monotherapy every 6 weeks for up to 3 years or until disease progression.
The trial had dual-primary endpoints that were PFS in both the dMMR/MSI-H and overall populations, and OS in the overall population. At this second interim analysis, pre-specified analyses of OS in the dMMR/MSI-H and MMRp/MSS populations were conducted. Safety assessment was a secondary endpoint.
About 494 patients were randomized (245 dostarlimab+CP; 249 PBO+CP). The trial achieved the dual-primary endpoint for OS at this second interim analysis. In the overall population, with 51.2% maturity, there was a significant 31% reduction in the risk of death favoring dostarlimab (HR 0.69; 95% CI 0.539–0.890; P=0.002). This crossed the pre-specified stopping boundary for OS (P=0.01101).
Subsequent immunotherapy was received by 17.1% of patients in the dostarlimab arm and 38.2% in the PBO arm. A clinically meaningful improvement of 16.4 months in median OS was observed in the dostarlimab arm compared to the PBO arm (44.6 mo vs 28.2 mo).
In the dMMR/MSI-H population, with 39.8% maturity, the HR for OS was 0.32 (95% CI 0.166–0.629), with median OS not reached in the dostarlimab arm and 31.4 months in the PBO arm. In the MMRp/MSS population, with 54.8% maturity, the HR for OS was 0.79 (95% CI 0.602–1.044; median OS 34.0 mo vs 27.0 mo), with 37.0% of patients receiving subsequent immunotherapy in the PBO arm vs 17.7% in the dostarlimab arm.
Safety outcomes at this second interim analysis remained consistent with those observed during the initial interim analysis.
Dostarlimab + CP conferred a significant and clinically relevant overall survival (OS) advantage over CP alone in the overall population and notably in the dMMR/MSI-H subgroup. Additionally, in the MMRp/MSS population, median OS improved by 7 months with a 21% reduction in the risk of death.
These findings were consistent despite approximately 40% of patients in the PBO arm receiving subsequent immunotherapy across all populations.
The RUBY Part 1 trial represented the first demonstration of an OS benefit in patients with primary advanced or recurrent endometrial cancer, supporting the adoption of dostarlimab + CP as a standard of care in the first-line setting.
The trial was sponsored by Tesaro, Inc.
Source: https://sgo.planion.com/Web.User/AbstractDet?ACCOUNT=SGO&ABSID=587475&CONF=AM2024&CKEY=
Clinical Trial: https://clinicaltrials.gov/study/NCT03981796
Powell MA, Auranen AA, Willmott LJ, et al. (2024) “Overall survival among patients with primary advanced or recurrent endometrial cancer treated with dostarlimab plus chemotherapy in the ENGOT-EN6-NSGO/GOG-3031/RUBY Trial.” Presented at SGO 2024.
