Antibody-drug conjugates for urothelial carcinoma

The standard of care for advanced urothelial carcinoma includes platinum chemotherapy and immunotherapy. Antibody-drug conjugates (ADCs), originally developed for hematologic malignancies, involve potent cytotoxic agents linked to antibodies that recognize tumor-specific antigens; this rational drug design allows for more on-target efficacy, while mitigating systemic toxicity. Herein, we review the emerging landscape of ADCs in urothelial carcinoma. The anti-Nectin-4 ADC enfortumab vedotin has demonstrated efficacy in prospective studies in patients with advanced urothelial carcinoma in several settings either alone or in combination with pembrolizumab. The anti-Trop-2 ADC sacituzumab govitecan has also shown efficacy in single-armed studies. Both conjugates have full or accelerated approval from the Food and Drug Administration. Common adverse events include rash and neuropathy for enfortumab vedotin and myelosuppression and diarrhea for sacituzumab govitecan. Several anti-human epidermal growth factor receptor 2 ADCs are in clinical trials, and in localized bladder cancer, the anti-epithelial cell adhesion molecule ADC oportuzumab monatox is being studied in patients refractory to intravesical bacillus calmette-guerin therapy. Antibody-drug conjugates for urothelial carcinoma are approved and emerging as therapies for patients with advanced urothelial carcinoma, filling a prior void for treatment of progressive disease. Ongoing studies are also evaluating these agents in the neoadjuvant and adjuvant settings.