Antibody–drug conjugates for the treatment of urothelial carcinoma

Abstract

ABSTRACT Introduction The therapeutic landscape for urothelial carcinoma has changed significantly over the past few years with the addition of immunotherapy to platinum-based chemotherapy. Targeted therapy against FGFR (fibroblast growth factor receptor) is now also approved for the minority of patients with FGFR aberrations. Antibody–drug conjugates (ADCs) are of great interest in urothelial carcinoma, with a recent FDA approval for enfortumab vedotin (EV) and others in development. Areas covered This review will provide an overview of treatment of advanced urothelial carcinoma and detail the various ADCs being studied in this disease. Expert opinion ADCs are an important therapeutic option for urothelial carcinoma. Responses to EV exceeded 40% in heavily pre-treated patients, while the response rate to EV combined with pembrolizumab in a phase 1b trial was ~70% in treatment-naïve patients. EV has already been approved in the United States and we await randomized data to confirm a survival benefit with EV. Meanwhile, studies of other ADCs, including in biomarker-selected populations, are ongoing. ADCs will undoubtedly play an increasing role in the management of urothelial carcinoma and will likely be offered earlier in the disease course, resulting in significant changes to treatment algorithms in urothelial cancer in the coming years.