Sequential therapies for advanced urothelial cancer: Hope meets new challenges

A dramatic change in the treatment of advanced urothelial carcinomas (UC) occurred in the last 3 years, initially with the development of several check-point inhibitors, for second and first-line therapy. More recently, the approval of anti-FGFR (Fibroblast Growth Factor Receptor) and anti-nectin-4 inhibitors based on phase 2 studies in refractory disease, and the preliminary results of 3 randomized phase 3 trials combining chemotherapy and immunotherapy in first-line as well as using maintenance immunotherapy after chemotherapy induction, created a new paradigm in the treatment of metastatic disease. In this review, we will explore the new classes of agents and how they could be incorporated in the clinical practice as well as the results of recently presented randomized studies, guiding oncologists on the possible sequences for patients with advanced urothelial carcinoma.