Current Status and Future Direction of Immunotherapy in Urothelial Carcinoma.

Since 2016, five new programmed cell death protein 1/ligand 1 (PD-1/L1) checkpoint inhibitors have been approved for metastatic urothelial carcinoma. This review will summarize the data supporting the widespread use of these agents and highlight areas of ongoing clinical development. PD-1/L1 axis inhibition has demonstrated clear superiority to chemotherapy for the treatment of metastatic urothelial cancer in the second-line setting. A multitude of ongoing studies are investigating the feasibility and efficacy of incorporating established and novel immunotherapies into earlier lines of therapy, including non-metastatic muscle-invasive bladder cancer and even non-muscle-invasive disease. Early-phase clinical trials have begun to explore the safety and activity of novel immune-oncology combinations across a range of clinical settings. Immunotherapy has a clearly defined role in the treatment of metastatic urothelial cancer both in the platinum-refractory setting and in the first-line cisplatin-ineligible setting. Ongoing clinical trials will dictate how to best incorporate immunotherapy into earlier lines of therapy and define the safety and activity of novel immunotherapy agents and combinations.