Enfortumab Vedotin for Urothelial Cancer

First-Line Treatment Setting

The National Comprehensive Cancer Network recommends enfortumab vedotin 1.25 mg/kg on Days 1 and 8 of a 21-day cycle, combined with pembrolizumab 200 mg on Day 1 of each 21-day cycle, as the preferred first-line treatment for locally advanced or metastatic urothelial cancer, regardless of cisplatin eligibility or PD-L1 status, with a median overall survival of 31.5 months versus 16.1 months with platinum-based chemotherapy 1, 2
This combination is the only Category 1, preferred first-line regimen for both cisplatin-eligible and cisplatin-ineligible patients, with no PD-L1 testing required for this indication 2, 3
Median progression-free survival is 12.5 months versus 6.3 months with chemotherapy, and median overall survival is 31.5 months versus 16.1 months with chemotherapy, with an objective response rate of 67.7% versus 44.4% with chemotherapy 1, 2

Enfortumab vedotin 1.25 mg/kg on Days 1, 8, and 15 of a 28-day cycle is a preferred subsequent-line systemic therapy option, with a confirmed objective response rate of 44% and a median overall survival of 12.88 months versus 8.97 months with chemotherapy 4, 6

Rash and peripheral neuropathy are common adverse events, with a incidence of 48-49% and 50%, respectively, and require monitoring and management 4, 3
Hyperglycemia is a common adverse event, with a Grade 3 incidence of 6.1%, and requires baseline screening and management with metformin or insulin therapy 7

Gemcitabine plus cisplatin or carboplatin is an alternative first-line option for cisplatin-eligible patients, with a median OS of 21.7 months versus 18.9 months with chemotherapy alone 2
Pembrolizumab or atezolizumab monotherapy is an alternative first-line option for cisplatin-ineligible patients with PD-L1 positive tumors, requiring PD-L1 testing 3