Evolving Therapies for Urothelial Carcinoma —Novel Paradigms and Future Directions

Within the last 5 years, multiple therapeutic options have been approved for the treatment of locally advanced and metastatic urothelial carcinoma. The standard of care for first-line therapy remains cisplatin-based chemotherapy; however, a significant number of patients are ineligible for treatment with cisplatin-based therapy. Immune checkpoint inhibitors have been approved for use in both the first-line (pembrolizumab and atezolizumab) and second-line (atezolizumab, durvalumab, avelumab, nivolumab, and pembrolizumab) settings for cisplatin-ineligible patients who are either programmed death-ligand 1-positive or are unable to tolerate chemotherapy. Recent data also establish maintenance immunotherapy as a new standard of care for platinum-eligible patients in the front-line setting. Here, we review the role of immunotherapeutic agents in locally advanced and metastatic urothelial carcinoma, along with the role of maintenance immunotherapy post-platinum-based chemotherapy, ongoing trials of combination immunotherapy and chemotherapy, antibody–drug conjugates, and fibroblast growth factor receptor-targeted therapy options for patients who are refractory to, or ineligible for, platinum-based therapy.