FDA Approves Durvalumab With Chemotherapy for Mismatch Repair–Deficient Primary Advanced or Recurrent Endometrial Cancer

Efficacy was evaluated in DUO-E (NCT04269200), a randomized, multicenter, double-blind, placebo-controlled trial in patients with primary advanced or recurrent endometrial cancer. Tumor MMR status was a stratification factor and was assessed using an immunohistochemistry tumor tissue test. Patients were randomized 1:1:1 to receive either:

• Durvalumab 1,120 mg with carboplatin plus paclitaxel every three weeks for a maximum of six cycles. Following completion of chemotherapy, patients received durvalumab 1,500 mg every four weeks as maintenance until they experienced disease progression.
• Placebo with carboplatin and paclitaxel every three weeks for a maximum of six cycles. Following completion of chemotherapy, patients received placebo every four weeks until they experienced disease progression.
• An additional investigational combination regimen.

The major efficacy outcome measure was progression-free survival (PFS), determined by investigator assessment using RECIST v1.1.

Although the researchers observed a statistically significant improvement in PFS in the overall population for durvalumab with carboplatin plus paclitaxel compared to carboplatin and paclitaxel alone, they attributed the improvement in the overall population primarily to patients with dMMR tumors based on an exploratory analysis by tumor MMR status.

In 95 patients with dMMR tumors, median PFS was not reached (NR) (95% CI = NR, NR) in the durvalumab arm and was 7 months (95% CI = 6.7, 14.8) in the placebo arm (hazard ratio = 0.42 [95% CI = 0.22, 0.80]). Overall survival, an additional efficacy outcome measure, was immature at the time of the PFS analysis.

The most common adverse reactions reported in more than 25% of patients receiving durvalumab in combination with carboplatin and paclitaxel were peripheral neuropathy, musculoskeletal pain, nausea, alopecia, fatigue, abdominal pain, constipation, rash, diarrhea, vomiting, and cough. View the prescribing information (https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761069s045lbl.pdf) for a complete list of adverse reactions.

The recommended durvalumab dose for patients with a body weight of at least 30 kg is 1,120 mg with carboplatin plus paclitaxel every three weeks for six cycles followed by single-agent durvalumab 1,500 mg every four weeks. The recommended durvalumab dose for patients with a body weight of less than 30 kg is 15 mg/kg with carboplatin and paclitaxel every three weeks for six cycles followed by durvalumab 20 mg/kg every four weeks. View the full prescribing information for durvalumab (https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761069s045lbl.pdf).

FDA’s review used the Assessment Aid (https://www.fda.gov/about-fda/oncology-center-excellence/assessment-aid), a voluntary submission from the applicant.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) or by calling 800-FDA-1088.

For assistance with single-patient applications for investigational oncology products, healthcare professionals may contact the Oncology Center of Excellence’s Project Facilitate (https://www.fda.gov/about-fda/oncology-center-excellence/project-facilitate) at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov (mailto:OncProjectFacilitate@fda.hhs.gov).