Antibody-Drug Conjugates in Urothelial Carcinomas

Urothelial carcinoma (UC) is a common malignancy with an urgent need for more effective and less toxic treatment strategies. Antibody-drug conjugate (ADC) represents a novel therapeutic approach, which combines the high specificity of monoclonal antibodies covalently linked with highly active cytotoxic agents. UC is an appropriate candidate for these drugs, as it expresses unique cell surface antigens that allow for specific targeting of these cells. We hereby present a review of the current literature and future perspectives of ADC treatment in early-stage and metastatic UC.

Several ADCs are in advanced stages of development and approval, such as intravesical oportuzumab monatox in BCG-refractory non-muscle invasive bladder cancer and enfortumab vedotin and sacituzumab govitecan in pretreated metastatic UC. Other agents are in earlier stages of development, including some promising anti-Her2 agents. The favorable toxicity profile of these agents led to several combination strategies, especially with checkpoint inhibitors. In light of the encouraging results presented in this review and the recent FDA approval of enfortumab vedotin, ADCs will likely be incorporated in the management of UC in the near future.