Behind the FDA Approval of Dostarlimab/Chemo for dMMR/MSI-H Endometrial Cancer

Matthew Powell, MD, professor, Obstetrics and Gynecology and chief, Division of Gynecologic Oncology, Siteman Cancer Center, Washington University School of Medicine, discusses findings from the phase 3 RUBY/ENGOT-EN6/GOG3031/NSGO (NCT03981796) study which led to the FDA approval of dostarlimab (Jemperli) in combination with chemotherapy for the treatment of patients with mismatch repair deficient/microsatellite instability-high primary advanced or recurrent endometrial cancer.

The global, double-blind, multicenter RUBY study randomized 494 patients to receive either treatment with dostarlimab plus chemotherapy (n = 245) or placebo. Among those enrolled, 47.8% had recurrent disease, 18.6% had primary stage III disease, and 33.9% had primary stage IV disease.

Dostarlimab was given at a dose of 500 mg plus carboplatin at a dose of the area under the curve of 5 mg/mL/minute and paclitaxel at a dose of 175 mg/m2 every 3 weeks for a total of 6 cycles. After the combination was given, maintenance dostarlimab was administered to patients at a dose of 1000 mg every 6 weeks for up to 3 years. In the control arm, patients received the same regimen with a matched placebo instead of dostarlimab.

Findings from the study demonstrated that the addition of dostarlimab to the standard chemotherapy combination of carboplatin and paclitaxel led to better outcomes compared with placebo with carboplatin and paclitaxel.

This approval for dostarlimab plus chemotherapy expands the indication for dostarlimab.

Transcription:

0:10 | The findings of the RUBY trial were really that substantial benefit of a 71% reduction of progression or death in our patients with deficient mismatch repair and similar overall benefits with a nice benefit for both patients with deficient mismatch repair and proficient mismatch repair. The entire population showed a benefit with the addition of the dostarlimab to carboplatin and paclitaxel.

0:39 | This really is transformative, this plus another trial that was done, both are consistent and show that really adding checkpoint inhibition to the upfront treatment for patients with advanced recurrent endometrial cancer is really the new standard of care.