KEY TAKEAWAYS
- The phase 3 RUBY study investigated the efficacy of combined chemotherapy and immunotherapy for endometrial cancer treatment.
- Progression-free survival and overall survival were the primary objectives.
- The study demonstrated that combining dostarlimab with carboplatin and paclitaxel improves progression-free survival for patients with advanced or recurrent endometrial cancer, particularly those with dMMR-MSI-H tumors.
The phase 3 double-blind, randomized, placebo-controlled clinical trial analyzed the effectiveness of combining chemotherapy and immunotherapy in endometrial cancer. The study enrolled primary advanced stage III or IV or first recurrent endometrial cancer patients. The patients (pts) were randomly assigned in 1:1 to receive either dostarlimab (500 mg) or placebo along with carboplatin and paclitaxel, administered every 3 weeks (for six cycles). This was followed by dostarlimab (1000 mg) or placebo every 6 weeks, maintained for up to 3 years. The primary objectives consisted of progression-free survival (PFS) and overall survival. The evaluation of safety was also conducted.
Of the 494 patients who were part of the randomization process, 118 individuals (23.9%) had tumors characterized by mismatch repair deficiency (dMMR) and high microsatellite instability (MSI-H). Within this subgroup of patients with dMMR-MSI-H tumors, the estimated progression-free survival (PFS) rate at the 24-month mark was 61.4% (95% confidence interval [CI]: 46.3 to 73.4) in the arm receiving dostarlimab, contrasting with 15.7% (95% CI: 7.2 to 27.0) in the placebo arm. The hazard ratio for progression or death was 0.28 (95% CI: 0.16 to 0.50; P<0.001). Across the entire patient cohort, the PFS rate was 36.1% (95% CI: 29.3 to 42.9) at 24 months for those in the dostarlimab arm and 18.1% (95% CI: 13.0 to 23.9) for the placebo arm. The hazard ratio for this comparison was 0.64 (95% CI: 0.51 to 0.80; P<0.001). Moreover, at the 24-month mark, the overall survival rate was 71.3% (95% CI: 64.5 to 77.1) for the dostarlimab treatment arm. It was 56.0% (95% CI: 48.9 to 62.5) for the placebo arm. The hazard ratio for mortality was 0.64 (95% CI: 0.46 to 0.87). The most prevalent adverse events (AEs) that occurred or worsened during the treatment course encompassed nausea (53.9% in the dostarlimab arm and 45.9% in the placebo arm), alopecia (53.5% and 50.0%), and fatigue (51.9% and 54.5%). Notably, severe and consequential adverse events were more frequent in the dostarlimab-treated arm than in the placebo-treated arm.
The study reported that the dostarlimab plus carboplatin-paclitaxel substantially enhanced PFS within the primary advanced or recurrent endometrial cancer patient subset, demonstrating a noteworthy advantage specifically among those with dMMR-MSI-H tumors.
Source: https://pubmed.ncbi.nlm.nih.gov/36972026/
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03981796
Mirza MR, Chase DM, Slomovitz BM, dePont Christensen R, Novák Z, Black D, Gilbert L, Sharma S, Valabrega G, Landrum LM, Hanker LC, Stuckey A, Boere I, Gold MA, Auranen A, Pothuri B, Cibula D, McCourt C, Raspagliesi F, Shahin MS, Gill SE, Monk BJ, Buscema J, Herzog TJ, Copeland LJ, Tian M, He Z, Stevens S, Zografos E, Coleman RL, Powell MA; RUBY Investigators. Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer. N Engl J Med. 2023 Jun 8;388(23):2145-2158. doi: 10.1056/NEJMoa2216334. Epub 2023 Mar 27. PMID: 36972026.
