FDA Approves Durvalumab Plus Carboplatin and Paclitaxel for Patients With Mismatch Repair Deficient Primary Advanced or Recurrent Endometrial Cancer

On June 14, 2024, the US Food and Drug Administration (FDA) approved durvalumab plus carboplatin and paclitaxel followed by durvalumab maintenance for patients with primary advanced or recurrent mismatch repair deficient (dMMR) endometrial cancer. This approval was based on results from the phase 3 DUO-E trial. 

In this double-blind, placebo-controlled trial, patients with primary advanced or recurrent endometrial cancer were stratified based on tumor MMR status and randomized on a 1-to-1-to-1 basis to receive 1120 mg of durvalumab with carboplatin and paclitaxel every 3 weeks for a maximum of 6 cycles followed by 1500 mg of durvalumab maintenance every 4 weeks until disease progression, or placebo plus carboplatin and paclitaxel every 3 weeks for a maximum of 6 cycles followed by placebo every 4 weeks, or an additional investigational combination regimen. The major efficacy outcome measure was progression-free survival (PFS). An additional efficacy outcome measure was overall survival (OS). 

In the overall population, durvalumab significantly improved PFS but this improvement was primarily attributed to patients with dMMR tumors. In the dMMR population, median PFS was not reached in the durvalumab arm and was 7 months in the placebo arm. OS was immature at the time of PFS analysis. The most common adverse reactions occurring in >25% of patients included peripheral neuropathy, musculoskeletal pain, nausea, alopecia, fatigue, abdominal pain, constipation, rash, diarrhea, vomiting, and cough. 

For patients with a body weight ≥30 kg, the recommended dose of durvalumab is 1120 mg plus carboplatin and paclitaxel every 3 weeks for 6 cycles followed by 1500 mg of durvalumab maintenance every 4 weeks. For patients with a body weight <30 kg the recommended dose of durvalumab is 15 mg/kg plus carboplatin and paclitaxel every 3 weeks for 6 cycles followed by 20 mg/kg of durvalumab maintenance every 4 weeks. 

Source:

FDA approves durvalumab with chemotherapy for mismatch repair deficient primary advanced or recurrent endometrial cancer. Published online: June 14, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-chemotherapy-mismatch-repair-deficient-primary-advanced-or-recurrent