FDA Approves Dostarlimab Plus Carboplatin and Paclitaxel for Advanced or Recurrent dMMR/MSI-H Endometrial Cancer

On July 31, 2023, The US Food and Drug Administration (FDA) approved dostarlimab-gxly plus carboplatin and paclitaxel for adult patients with advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H), as detected by an FDA-approved test.

This approval was based on results from the randomized, multicenter, double blind RUBY trial. In this trial, patients were randomized on a 1-to-1 basis to receive either 500 mg dostarlimab, administered every 3 weeks, with carboplatin and paclitaxel, followed by 1000 mg dostarlimab, or placebo with carboplatin and paclitaxel, followed by placebo. Treatment was administered in 6 doses until disease progression, unacceptable toxicity, or up to 3 years. Patients were stratified by MMR/MSI status, presence of prior external pelvic radiotherapy, and disease status.

The efficacy was based on investigator-assessed progression-free survival (PFS) in a pre-specified subgroup of 122 patients with MMR/MSI tumor status using RECIST v 1.1 guidelines. The median PFS in the dostarlimab arm was 30.3 months compared to 7.7 months in the placebo arm (hazard ratio, 0.29; 95% CI, 0.17 to 0.50; P < .0001), representing a statistically significant improvement.

The most common adverse events occurring in ≥ 20% of patients included rash, diarrhea, hypothyroidism, and hypertension. The most common immune-mediated adverse reactions were pneumonitis, colitis, hepatitis, endocrinopathies, such as hypothyroidism, nephritis with renal dysfunction, and skin adverse reactions.

The recommended dose is 500 mg dostarlimab every 3 weeks for 6 doses with carboplatin and paclitaxel, followed by 1000mg monotherapy every 6 weeks until disease progression or unacceptable toxicity, or up to 3 years. Dostarlimab should be administered before chemotherapy when administered on the same day.

Source:
FDA approves dostarlimab-gxly with chemotherapy for endometrial cancer. United States Food and Drug Administration. July 31, 2023. Accessed August 1, 2023. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-dostarlimab-gxly-chemotherapy-endometrial-cancer