Durvalumab Plus Chemotherapy Wins FDA Approval in dMMR Endometrial Cancer

• Durvalumab (Imfinzi) with carboplatin plus paclitaxel, followed by single-agent durvalumab, is now FDA-approved for adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR).
• Findings from the phase 3 DUO-E trial (NCT04269200) support this regulatory decision.
• The study demonstrated a significant improvement in progression-free survival (PFS) for patients with dMMR tumors.

The FDA approved the combination of durvalumab (Imfinzi) with carboplatin plus paclitaxel, followed by single-agent durvalumab, for the treatment of adult patients with primary advanced or recurrent endometrial cancer that is dMMR.¹

The basis of this approval is supported by findings from the phase 3 DUO-E trial. Here, patients with dMMR tumors had a median PFS that was not reached (NR; 95% CI, NR-NR) in the durvalumab arm vs 7 months (95% CI, 6.7-14.8) in the placebo arm (HR, 0.42; 95% CI, 0.22-0.80).

“The bottom line is our primary analysis was positive, and that combination does work more than the control arm of chemotherapy,” Shannon Westin, MD, MPH, FACOG, director, Early Drug Development, and professor, Department of Gynecologic Oncology and Reproductive Medicine, Division of Surgery, The University of Texas MD Anderson Cancer Center, previously told Targeted Oncology^TM, in an interview.

Gynecologic Cancer Illustration: © Crystal Light - stock.adobe.com

According to the press release, the FDA stated that while there was a statistically significant improvement in PFS seen among patients treated with the durvalumab regimen in the overall population (HR, 0.71; 95% CI, 0.57 to 0.89; P = .003), the improvement was linked to patients with dMMR tumors, based on an exploratory analysis of MMR status.^1,2

For safety, the most common adverse events seen in >25% patients with the combination included peripheral neuropathy, musculoskeletal pain, nausea, alopecia, fatigue, abdominal pain, constipation, rash, diarrhea, vomiting, and cough. The prescribing information provides the complete adverse reactions.

About the DUO-E Trial

DUO-Eis a global, double-blind, placebo-controlled trial. Enrollment was open to patients aged 18 years or older with newly diagnosed advanced stage III/IV or recurrent endometrial cancer of epithelial histology, excluding sarcomas, and patients were required to have known MMR status.²

The study randomized patients in a 1:1:1 fashion to receive either durvalumab plus carboplatin/paclitaxel followed by durvalumab monotherapy, placebo plus carboplatin/paclitaxel followed by maintenance placebo, or durvalumab plus carboplatin/paclitaxel followed by maintenance durvalumab plus olaparib (Lynparza).

The recommended dose of durvalumab is 1120 mg with carboplatin given with paclitaxel every 3 weeks for 6 cycles, followed by durvalumab as a single agent at a dose of 1500 mg every 4 weeks in patients with a body weight of at least 30 kg. For those with a body weight of less than 30 kg, durvalumab is recommended at a dose of 15 mg/kg in combination with carboplatin and paclitaxel every 3 weeks for 6 cycles, followed by 20 mg/kg of durvalumab every 4 weeks.

REFERENCES:

1. FDA approves durvalumab with chemotherapy for mismatch repair deficient primary advanced or recurrent endometrial cancer. FDA. June 14, 2024. Accessed June 14, 2024. https://tinyurl.com/3dee6kjf

2. Westin SN, Moore K, Chon HS, et al. Durvalumab plus carboplatin/paclitaxel followed by maintenance durvalumab with or without olaparib as first-line treatment for advanced endometrial cancer: the phase III DUO-E trial. J Clin Oncol. 2024;42(3):283-299. doi:10.1200/JCO.23.02132