Targeted and immunotherapy for the management of advanced urothelial carcinoma of the bladder.

The article reviews the activity and approval status of targeted therapies and immunotherapies for advanced urothelial bladder cancer, focusing on six FDA-approved agents. Platinum-based chemotherapy remains the standard first-line treatment, while pembrolizumab (a programmed cell death 1 [PD-1] inhibitor) is approved as first-line therapy for patients ineligible for platinum chemotherapy, alone or combined with enfortumab vedotin (an antibody-drug conjugate targeting nectin-4) for cisplatin-ineligible patients. Avelumab (a programmed death ligand 1 [PD-L1] inhibitor) is approved for maintenance therapy after first-line platinum chemotherapy, and pembrolizumab, avelumab, and nivolumab (another PD-1 inhibitor) are approved for second-line treatment following progression. Erdafitinib, a fibroblast growth factor receptor (FGFR) inhibitor, is indicated for patients with FGFR2 or FGFR3 genetic alterations after platinum therapy, while enfortumab vedotin and sacituzumab govitecan (an antibody-drug conjugate targeting Trop-2) are approved for patients previously treated with platinum chemotherapy and PD-1/PD-L1 inhibitors. The article highlights ongoing confirmatory trials to establish the precise roles of these agents in treatment sequencing and combination strategies.