Progress of antibody-drug conjugates in the treatment of locally advanced or metastatic urothelial carcinoma: opportunities and challenges.

Objective: The objective of this review is to provide an overview of the clinical progress, administration methods, efficacy, safety, and treatment-related adverse events associated with antibody-drug conjugates.

Results: Locally advanced or metastatic urothelial carcinoma is an aggressive and lethal malignancy. Cisplatin-based chemotherapy has been the first-line therapy for most patients over the past two decades. However, approximately 50% of patients with locally advanced or metastatic urothelial carcinoma are ineligible for cisplatin-based chemotherapy due to inadequate renal function, poor performance status, or complications. Furthermore, patients who exhibit suboptimal responses or disease progression following platinum-based chemotherapy face therapeutic uncertainty regarding the selection of alternative agents. The emergence of antibody-drug conjugates has provided new options for patients afflicted with this disease, particularly enfortumab vedotin combined with pembrolizumab as a new first-line therapy for advanced urothelial carcinoma or for patients ineligible for platinum-based therapy. Additionally, in the TROPICS-04 trial, sacituzumab govitecan failed to demonstrate significant improvement in overall survival or progression-free survival compared with the physician's choice of treatment for patients with advanced urothelial carcinoma progressing after platinum-based chemotherapy and PD-(L)1 inhibitor therapy; the FDA withdrew its approval for this indication. ADCs are also being considered for the treatment of muscle-invasive bladder cancer, with ongoing clinical trials.