Targeted Therapies in Advanced and Metastatic Urothelial Carcinoma

SIMPLE SUMMARY: Urothelial carcinoma is a malignancy of the cells lining the genitourinary tract but it most commonly occurs in the bladder. Once urothelial carcinoma has spread outside of the genitourinary tract, survival outcomes are poor despite the standard of care treatment of chemotherapy followed by immunotherapy. Genetic sequencing of cancer tissue has identified targets for new anti-cancer drugs. This review summarizes the evidence regarding the efficacy of targeted therapies in advanced urothelial carcinoma. ABSTRACT: This review describes the current landscape of targeted therapies in urothelial carcinoma. The standard of care for advanced urothelial carcinoma patients remains platinum-based combination chemotherapy followed by immunotherapy. However, median overall survival for these patients is still <1 year and there is an urgent need for alternative therapies. The advent of next-generation sequencing has allowed widespread comprehensive molecular characterization of urothelial tumors and, subsequently, the development of therapies targeting specific molecular pathways implicated in carcinogenesis such as FGFR inhibition, Nectin-4, Trop-2, and HER2 targeting. As these therapies are demonstrated to be effective in the second-line setting, they will be advanced in the treatment paradigm to localized and even non-muscle invasive disease.