Durvalumab With Chemotherapy Approved for Mismatch Repair–Deficient Primary Advanced or Recurrent Endometrial Cancer
Expert Perspectives · Lyn Brook · 2024-06-17
The FDA has granted approval to durvalumab (Imfinzi®, AstraZeneca UK Limited) with carboplatin plus paclitaxel followed by single-agent durvalumab for adult patients with primary advanced or recurrent mismatch repair–deficient (dMMR) endometrial cancer.
Why it matters: “Immunotherapy and chemotherapy combinations have shown activity in endometrial cancer, with greater benefit in dMMR than MMR-proficient (pMMR) disease,” wrote Shannon Westin, MD, MPH, the Director of Early Drug Development in the Gynecologic Oncology Department at MD Anderson Cancer Center, and colleagues, in their published results of the DUO-E trial (NCT04269200), on which approval was based. “Adding a poly (ADP-ribose) polymerase inhibitor may improve outcomes, especially in pMMR disease.”
What they studied: Efficacy was assessed in the phase 3, double-blind, placebo-controlled, multicenter trial in which patients with primary advanced or recurrent endometrial cancer were randomized 1:1:1 to receive either:
- 1,120 mg of durvalumab with carboplatin plus paclitaxel every three weeks for a maximum of six cycles. Upon completion of chemotherapy, patients received 1,500 mg of durvalumab every four weeks as maintenance until disease progression
- Placebo with carboplatin and paclitaxel every three weeks for a maximum of six cycles. Upon completion of chemotherapy, patients received placebo every four weeks until disease progression
- An additional investigational combination regimen including olaparib
Stratification was based on an immunohistochemistry tumor tissue test to assess patients’ tumor MMR status.
The primary efficacy outcome measured was progression-free survival, determined by investigator assessment using RECIST v1.1.
What they found: Statistically significant improvement was observed in progression-free survival in the overall population for durvalumab and carboplatin plus paclitaxel compared with carboplatin and paclitaxel alone. This improvement was primarily seen due to the observation of patients with dMMR tumors based on an exploratory analysis by tumor MMR status.
The median progression-free survival in 95 patients with dMMR tumors receiving durvalumab was not reached. The median progression-free survival in the placebo arm was 7 months. In addition, overall survival was assessed as a secondary efficacy outcome but was immature at the time of progression-free survival analysis.
Adverse events: The most common adverse events experienced by >25% receiving durvalumab in combination with carboplatin and paclitaxel were peripheral neuropathy, musculoskeletal pain, nausea, alopecia, fatigue, abdominal pain, constipation, rash, diarrhea, vomiting, and cough. The prescribing information provides the complete adverse reactions.
Conclusion: “Carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab with or without olaparib demonstrated a statistically significant and clinically meaningful progression-free survival benefit in patients with advanced or recurrent endometrial cancer,” concluded Dr. Westin and colleagues.
Instructions: The recommended dosage of durvalumab for patients with a body weight ≥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 <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.