Antibody–drug conjugates in urothelial carcinoma: current status and future

Antibody-drug conjugates (ADCs) are quickly becoming frontline standard of care in many tumor types, including urothelial carcinoma. This review summarizes recent clinical investigations into the use of ADCs targeting nectin-4, trophoblast cell surface antigen-2 (Trop-2), human epidermal growth factor receptor 2 (HER-2), and other antigens in urothelial carcinoma. This review covers efficacy and toxicity data of ADCs alone and in combination with immunotherapy; mechanisms of resistance; and preclinical studies that provide biological basis for clinical approaches. Enfortumab vedotin and sacituzumab govitecan can be used in an unselected group of patients with urothelial carcinoma whereas HER-2 ADCs have only been administered in those with high expression or amplification. Most are being studied in combination with immune checkpoint inhibitors. Data supports use of enfortumab vedotin in combination with pembrolizumab as first-line therapy in metastatic/unresectable locally advanced urothelial carcinoma. Sacituzumab govitecan may be used as later-line option in these patients. HER-2 therapy is still under investigation but has many recent promising results.