Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer: Outcomes by Blinded Independent Central Review of the RUBY trial (ENGOT-EN6-NSGO/GOG3031/RUBY)
Matthew Powell, MD, presents data from the blinded independent central review of the RUBY trial, which studied dostarlimab in patients with primary advanced or recurrent endometrial cancer.
Background
Dostarlimab plus carboplatin/paclitaxel led to statistically significant and clinically meaningful improvement in PFS by INV per RECIST v1.1 with an early OS trend
Overall Population, OS HR 0.64; 95% CI, 0.46–0.87; P=0.0021a
Both INV and BICR assessment have been shown as valid estimates of treatment effect in endometrial cancer2-6
Concordance between both INV and BICR can provide more confidence in results
Methods
RUBY is a phase 3, global, randomized, double-blind, multicenter, placebo-controlled study.
Patients (pts) with primary advanced stage III or IV or first recurrent endometrial cancer were randomized 1:1 to receive dostarlimab 500 mg, or placebo, plus carboplatin AUC 5 and paclitaxel 175 mg/m2 Q3W (6 cycles), followed by dostarlimab 1000 mg, or placebo, monotherapy Q6W for up to 3 years.
Secondary endpoints by BICR assessment per RECIST v1.1 were PFS, ORR, DOR, and DCR in the overall and dMMR/MSI-H populations.
Results
494 pts were randomized (245:dostarlimab+carboplatin-paclitaxel; 249:placebo+carboplatin-paclitaxel); 47.8% had recurrent disease, 18.6% and 33.6% had primary stage III and IV disease, respectively.
PFS by BICR was longer with dostarlimab+carboplatin-paclitaxel than placebo+carboplatin-paclitaxel in the dMMR/MSI-H (HR 0.29; 95% CI 0.158–0.543) and overall populations (HR 0.66; 95% CI 0.517–0.853).
Consistent benefits were seen with dostarlimab+carboplatin-paclitaxel for ORR, DCR, and DOR by BICR in the dMMR/MSI-H and overall populations. Safety was previously reported.
Conclusions
Dostarlimab + carboplatin-paclitaxel demonstrated a statistically significant and clinically meaningful PFS benefit in the overall population, with a substantial, transformative benefit in patients with dMMR/MSI-H tumors.
PFS by BICR was consistent with PFS by INV.
Dostarlimab + carboplatin-paclitaxel reduced the risk of progression or death by 34% in the overall population and by 71% in the dMMR/MSI-H population when assessed by BICR.
PFS results by BICR showed high concordance with PFS by INV.
Overall, efficacy assessments by both INV and BICR, along with a manageable safety profile, support a favorable benefit/risk profile for dostarlimab + carboplatin-paclitaxel in patients with primary advanced or recurrent endometrial cancer.
Powell MA, Hietanen S, Coleman RL et al. Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer: Outcomes by Blinded Independent Central Review of the RUBY trial (ENGOT-EN6-NSGO/GOG3031/RUBY). Abstract presented at: 2023 ASCO Annual Meeting, June 2-6, 2023.