Enfortumab Vedotin Combo Is Approved by FDA for Advanced Urothelial Cancer
Patients with locally advanced or metastatic urothelial cancer may now receive enfortumab vedotin plus pembrolizumab following its approval by the FDA.
The News
Enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) has been approved by the FDA for patients with locally advanced or metastatic urothelial cancer, according to a press release from the organization.
Enfortumab Vedotin’s Efficacy
The median overall survival (OS) was 31.5 months (95% CI, 24.4-not estimable) in the combination arm and 16.1 months (95% CI, 10.4-18.3) in the chemotherapy arm. (HR, 0.47; 95% CI, 0.38-0.58; P <.0001). The median progression-free survival (PFS) was 12.5 months (95% CI, 10.4-16.6) vs 6.3 months (95% CI, 6.2-6.5) in each arm respectively (HR, 0.45; 95% CI, 0.38-0.54; P <.0001).
Patients with locally advanced or metastatic urothelial cancer may now receive enfortumab vedotin plus pembrolizumab following its approval by the FDA.
Safety
Frequent adverse effects among those treated in the combination arm included increased aspartate aminotransferase, increased creatinine, rash, and increased glucose.
The Phase 3 EV-302/KN-A39 Trial
The approval is based on results from the phase 3 EV-302/KN-A39 trial (NCT04223856), in which 886 patients in the aforementioned population who had not received prior systemic therapy for advanced disease were enrolled and randomly assigned 1:1 to either the combination arm or the platinum-based chemotherapy arm.
The study’s primary end points were OS and PFS by blinded independent central review. Secondary end points included objective response rate, time to pain progression, and mean change from baseline in worst pain at week 26. Patients were randomly assigned and stratified based on cisplatin eligibility, PD-L1 expression, and presence of liver metastases.
Patients were eligible for treatment if they had histologically documented unresectable locally advanced or metastatic urothelial carcinoma, measurable disease, and could receive either cisplatin- or carboplatin-containing regimens. Patients were excluded from the trial if they had previously received enfortumab, had prior PD-1/PD-L1 treatment, or prior treatment with an agent directed to another stimulatory or coinhibitory T-cell receptor.
The recommended dose of enfortumab vedotin in combination with pembrolizumab was 1.25 mg/kg given intravenously over 30 minutes on days 1 and 8 of a 21-day cycle. Pembrolizumab can be given at 200 mg intravenously every 3 weeks or 400 mg every 6 weeks until disease progression, unacceptable toxicity, or 2 years of therapy.
Reference
FDA approves enfortumab vedotin-ejfv with pembrolizumab for locally advanced or metastatic urothelial cancer. News release. FDA. December 15, 2023. Accessed December 15, 2023. https://bit.ly/48ls9bi
