Introduction: The therapeutic landscape of metastatic urothelial carcinoma (mUC) becomes increasingly dense: standard therapy remains cisplatin-based chemotherapy, followed by immunotherapy with checkpoint inhibitors as maintenance or second-line. New directions include erdafitinib, a fibroblast growth factor receptor (FGFR) inhibitor in patients with corresponding mutations in FGFR2/3 receptor. Enfortumab vedotin (EV) is an antibody-drug conjugate targeting nectin-4 and is conjugated with monomethyl auristatin E (MMAE). It received FDA approval based on phase I/II data recently and thus represents an alternative to established third-line chemotherapies with vinflunine, paclitaxel, or docetaxel.Areas covered: The aim of this review was to evaluate the added value of Enfortumab vedotin in the therapeutic landscape of mUC. Current therapeutic options and alternatives for the affected patients are described, followed by a detailed description of the characteristics and available results of EV. Ongoing studies are explained, the present significance of the substance is assessed and its further future potential is outlined.Expert opinion Enfortumab vedotin has shown encouraging efficacy and a good tolerability in phase I/II trials, especially in heavily pretreated patients and patients with liver metastases. It appears to outperform third-line chemotherapies; ongoing studies will show the future potential of EV in treatment sequence.
Keywords: Antibody-drug conjugate; bladder cancer; locally advanced urothelial cancer; metastatic urothelial cancer; nectin-4; systemic therapy.