Background: Many patients with locally advanced or metastatic urothelial carcinoma (mUC) need additional treatment options beyond PD-1 or PD-L1 inhibitors and platinum-based chemotherapies. Enfortumab vedotin-ejfv (EV) is an antibody–drug conjugate directed at Nectin-4 that received accelerated approval for treatment of adults with locally advanced or mUC previously treated with PD-1/PD-L1 inhibitors and platinum- containing chemotherapy in the neoadjuvant/adjuvant, locally advanced, or metastatic settings.

Objectives: This article provides practical considerations and recommendations regarding common and potentially treatment-limiting adverse events that may arise with EV therapy.

Methods: The clinical data that supported the approval of EV are reviewed, and supporting safety and management considerations are provided based on the authors’ experience.

Findings: EV therapy can be optimized through patient and caregiver education, proactive patient monitoring, early identification of adverse events, and timely intervention to alleviate symptoms.