FDA approves durvalumab with chemotherapy for mismatch repair deficient primary advanced or recurrent endometrial cancer
Regulatory approval: On June 14, 2024, the FDA approved durvalumab with carboplatin plus paclitaxel followed by durvalumab maintenance for adult patients with primary advanced or recurrent mismatch repair–deficient (dMMR) endometrial cancer. The decision was supported by DUO-E (NCT04269200), where an exploratory analysis in 95 patients with dMMR tumors showed median PFS not reached with durvalumab vs 7 months with placebo (HR 0.42; 95% CI, 0.22–0.80).
FDA approval (2024-06-14): durvalumab + chemotherapy in dMMR endometrial cancer
The US Food and Drug Administration (FDA) approved durvalumab (Imfinzi; AstraZeneca UK Limited) on June 14, 2024, in combination with carboplatin plus paclitaxel, followed by single-agent durvalumab, for adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR).
Supporting evidence
Efficacy and safety were 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.
The major efficacy endpoint was progression-free survival (PFS) by investigator assessment per RECIST v1.1. A statistically significant PFS improvement was observed in the overall population for durvalumab + chemotherapy vs chemotherapy alone; however, FDA noted that the overall benefit was primarily attributed to patients with dMMR tumors, based on an exploratory analysis.
In 95 patients with dMMR tumors, median PFS was not reached (95% CI: NR–NR) with durvalumab vs 7 months (95% CI: 6.7–14.8) with placebo (HR 0.42; 95% CI: 0.22–0.80). Overall survival was immature at the time of the PFS analysis.
Safety and dosing (label)
Common adverse reactions (>25%) included peripheral neuropathy, musculoskeletal pain, nausea, alopecia, fatigue, abdominal pain, constipation, rash, diarrhea, vomiting, and cough.
Recommended dosing: ≥30 kg: 1,120 mg q3w with chemotherapy for 6 cycles, then 1,500 mg q4w maintenance; <30 kg: 15 mg/kg q3w then 20 mg/kg q4w.