FDA Approves Dostarlimab-gxly With Chemotherapy for Patients With Endometrial Cancer

On July 31, 2023, the US Food and Drug Administration (FDA) granted approval to dostarlimab-gxly with carboplatin and paclitaxel for adults with advanced or recurrent endometrial cancer that is microsatellite instability-high (MSI-H) or is determined by an FDA-approved test to be mismatch repair deficient (dMMR). 

The FDA approval is based on results from the randomized, multicenter, double-blind, placebo-controlled RUBY/ENGOT-EN6/GOG3031/NSGO trial. A total of 122 patients with dMMR, advanced, or recurrent endometrial cancer were included in the analysis. Any patients that did not meet the qualifications to be included in this trial were excluded from the analysis.

The main outcome measure used in this trial was investigator-assessed progression-free survival (PFS), which was assessed by blinded independent central review that followed RECIST v 1.1 guidelines. 

A PFS improvement was observed in the dMMR/MSI-H group, with a median PFS of 30.3 vs 7.7 months (hazard ratio, 0.29; 95% confidence interval, 0.17 to 0.50; P < .0001) in the dostarlimab-gxly and placebo-containing groups, respectively.

The most common adverse reactions, which occurred in ≥20% of patients who received dostarlimab-gxly plus carboplatin and paclitaxel, were rash, diarrhea, hypothyroidism, and hypertension. The researchers also found that immune-mediated adverse reactions can occur with dostarlimab-gxly treatment, such as pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, and skin adverse reactions.

“As a clinician, I celebrate the practice-changing potential of adding [dostarlimab-gxly] to chemotherapy for patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer who have had limited treatment options. Based on the results from the RUBY clinical trial, I look forward to the addition of [dostarlimab-gxly] to chemotherapy becoming a new standard of care for patients,” said Matthew Powell, MD, chief of the Division of Gynecologic Oncology at Washington University School of Medicine and the US principal investigator of the RUBY trial.

The recommended dosage of dostarlimab-gxly as a single agent is 500 mg every 3 weeks for 4 doses, and it should be administered as an intravenous infusion over 30 minutes. After 3 weeks of treatment and dose 4, every 6 weeks a patient should be administered with 1000 mg until disease progression or unacceptable toxicity occurs. 

Sources:
FDA approves dostarlimab-gxly with chemotherapy for endometrial cancer. United States Food and Drug Administration. July 31, 2023. Accessed August 7, 2023. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-dostarlimab-gxly-chemotherapy-endometrial-cancer