Advanced urothelial cancer (aUC) is invariably lethal and standard of care, platinum-based chemotherapy has changed little over the past 25 years. However, the past 5 years have been transformational with the advent of immunotherapies and targeted therapies. In this review, the authors focus on the therapies that are showing the greatest promise and have changed, or will imminently impact, the treatment landscape of aUC. Checkpoint inhibition is showing deep and durable responses in some patients and trial activity is concentrated on identifying the most suitable position within the treatment paradigm along with the most appropriate patients and therapeutic combinations. Novel targeted therapies in aUC are gaining renewed interest with nectin-4 antibody drug conjugates and fibroblast growth factor receptor inhibitors, both receiving recent regulatory approvals. Bispecific antibodies, capable of binding to two targets at the same time, are also showing promise. This review discusses the preclinical data, the relevant past, and present clinical trials along with regulatory status to provide a concise overview of the current and impending treatment options for aUC.
