‘Unprecedented’ Results Support Dostarlimab Approval in Endometrial Cancer

In an interview with CancerNetwork^®, Brian Slomovitz, MD, MS, FACOG, spoke about “unprecedented” findings from the phase 3 RUBY trial (NCT03981796) that supported the FDA approval of dostarlimab (Jemperli) plus chemotherapy as a treatment for patients with primary advanced or recurrent mismatch repair deficient (dMMR) or microsatellite instability–high (MSI-H) endometrial cancer.¹

According to Slomovitz, a gynecologic oncologist, director of Gynecologic Oncology, and co-chair of the Cancer Research Committee at Mount Sinai Medical Center in Miami Beach, Florida and a professor of Obstetrics and Gynecology at Florida International University, the dostarlimab-based regimen produced similar benefits across the dMMR and intent-to-treat (ITT) populations in the RUBY trial. Additionally, he stated that there were plans to research the regimen further among all-comers and those with mismatch repair proficient (pMMR) disease.

According to a press release at the time of the dostarlimab regimen’s approval, the dMMR/DSI-H population experienced a 71% reduction in the risk of disease progression or death after receiving the dostarlimab regimen. Additionally, data presented at The Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer and published in New England Journal of Medicine^2,3 highlighted a 24-month progression-free survival rate of 61.4% (95% CI, 46.3%-73.4%) with the dostarlimab regimen vs 15.7% (95% CI, 7.2%-27.0%) with placebo plus chemotherapy in the dMMR/MSI-H group (HR, 0.28; 95% CI, 0.16-0.50; P <.001).

Transcript:

The bottom line of the RUBY trial is that we demonstrated that in patients with endometrial cancer, adding checkpoint inhibitors increased activity in the first or second line. More specifically in the [dMMR] population, the results were unprecedented. [There was an] HR of 0.30 [for overall survival and] a 70% to 72% reduction in the risk of recurrence in patients with dMMR tumors treated with checkpoint inhibitors. We also found that in the ITT population, there was a similar benefit. Again, [it was] unprecedented to find this just by adding a checkpoint inhibitor.

As mentioned, [these were] great results—some of the best results we've seen in gynecologic oncology—leading to the FDA approval of dostarlimab in combination with chemotherapy in patients with advanced recurrent metastatic disease [and] dMMR tumors. We're not done yet; we're looking at all-comers and pMMR [tumors]. But right now, that's where FDA approval stands.

References

1. Jemperli (dostarlimab) plus chemotherapy approved in the US as the first new frontline treatment option in decades for dMMR/MSI-H primary advanced or recurrent endometrial cancer. News release. GSK. July 31, 2023. Accessed August 3, 2023. https://shorturl.at/izGL9
2. Mirza M, Chase D, Slomovitz, et al. Dostarlimab in Combination with Chemotherapy for the Treatment of Primary Advanced or Recurrent Endometrial Cancer: a Placebo-Controlled Randomized Phase 3 Trial (ENGOT-EN6-NSGO/GOG-3031/RUBY). Presented at: 2023 SGO Annual Meeting on Women’s Cancer; March 25-28, 2023; Tampa, Florida.
3. Mirza MR, Chase DM, Slomovitz BM, et al. Dostarlimab for primary advanced or recurrent endometrial cancer. N Engl J Med. 2023;388(23):2145-2158. doi:10.1056/NEJMoa2216334