• Michael Lattanzi and Jonathan E Rosenberg.
• Department of Medicine, Memorial Sloan Kettering Cancer Center , New York, NY, USA.
• Expert Rev Anticancer Ther. 2020 Jul 1; 20 (7): 551-561.

IntroductionIn December 2019, the US Food and Drug Administration granted accelerated approval to the novel nectin-4-targeting antibody-drug conjugate, enfortumab vedotin, for the treatment of platinum-refractory and immune checkpoint blockade-refractory locally advanced or metastatic urothelial carcinoma. Antibody-drug conjugates represent a new therapeutic modality in urothelial cancer; and beyond nectin-4, agents targeting Trop-2, HER2, and EpCAM are also in clinical development.Areas CoveredThis review outlines the biologic rationale and the clinical development of novel antibody-drug conjugates for the treatment of urothelial cancer across the spectrum of disease from non-muscle-invasive bladder cancer through treatment-refractory metastatic disease.Expert OpinionThe high response rates observed with enfortumab vedotin - both as monotherapy and in combination with checkpoint blockade immunotherapy - suggest this and other antibody-drug conjugates may have efficacy similar to or even exceeding that of traditional cytotoxic chemotherapy. Ongoing clinical development of antibody-drug conjugates in urothelial cancer will address the optimal combination or sequencing strategy with anti-PD-1/L1 immunotherapy and platinum-based chemotherapy.

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