FDA Approves Dostarlimab Plus Chemotherapy for Patients With Primary Advanced or Recurrent Endometrial Cancer

On August 1, 2024, the US Food and Drug Administration (FDA) approved dostarlimab plus carboplatin and paclitaxel, followed by single-agent dostarlimab for patients with primary advanced or recurrent endometrial cancer. This regimen was previously approved for patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H). This expanded indication is based upon results from the phase 3 RUBY trial.

In this randomized, multi-center, double-blind, placebo-controlled trial, 494 patients were randomized on a 1-to-1 basis to receive either dostarlimab plus carboplatin and paclitaxel followed by dostarlimab, or placebo plus carboplatin and paclitaxel followed by placebo. All patients had primary advanced or recurrent endometrial cancer and randomization was stratified by mismatch repair/microsatellite instability status, prior external pelvic radiotherapy, and disease status. The major efficacy outcomes of this trial were progression-free survival (PFS) as assessed by investigator using RECIST v1.1 in the dMMR/MSI-H cohort and overall populations, and overall survival (OS) in the overall population.

There was a statistically significant improvement of overall survival (OS) within the overall population in the dostarlimab arm. The median OS in the dostarlimab arm was 44.6 months vs 28.2 months in the placebo arm (hazard ratio [HR], 0.69; 1-sided P = .002). The median PFS in the overall population was 11.8 months in the dostarlimab arm vs 7.9 month in the placebo arm (HR = 0.64; 1-sided P < .0001).

The most common adverse events, occurring in ≥20% of patients, with dostarlimab plus carboplatin and paclitaxel were anemia, increased creatinine, peripheral neuropathy, decreased white blood cell count, fatigue, nausea, alopecia, low platelets, increased glucose, lymphopenia, neutropenia, liver function test abnormalities, arthralgia, rash, constipation, diarrhea, decreased albumin, abdominal pain, dyspnea, decreased appetite, increased amylase, urinary tract infection, and vomiting.

The recommended dose of dostarlimab is 500 mg every 3 weeks for 6 cycles with carboplatin and paclitaxel, followed by 1000 mg alone every 6 weeks until disease progression or unacceptable toxicity, or up to 3 years. When administered on the same day as chemotherapy, dostarlimab should be administered first.

Source:

FDA expands endometrial cancer indication for dostarlimab-gxly with chemotherapy.Published online: August 1, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-expands-endometrial-cancer-indication-dostarlimab-gxly-chemotherapy