[New paradigms in the second line treatment for advanced and metastatic urothelial carcinoma.]

Until 2016, the treatment options for patients with urothelial carcinoma who had progressed to first line treatment were limited. Vinflunine has been the only approved treatment in Europe for this indication. The only alternatives in these patients were clinical trials or other chemotherapies with low efficacy and high toxicity. The last couple of years, three immune-checkpoint inhibitors have been approved in Europe (pembrolizumab, atezolizumab and nivolumab) and five in USA (pembrolizumab, atezolizumab, nivolumab, durvalumaband avelumab), showing improved overall survival (OS), response rate (ORR) and tolerance. Recently, the FDA has approved two new treatments based on the results from the phase II trials. Erdafitinib, the first anti-FGFR treatment in patients with mutations/fusions in FGFR2/3 showed an ORR of 40% and an OS of 13,8 months. Likewise, enfortumab-vedotin, an antibody conjugates, was approved by the FDA based on the phase II trial results. Enfortumab-vedotin presented an ORR of 44%(12% of complete response) and an OS of 11,7 months. Other antiFGFR, antibody conjugates and immunotherapy combinations are in development, with promising results that need to be further confirmed in order to be approved. As a result, the landscape of urothelial canceris rapidly evolving. However, the challenge of individualizing and sequencing treatments remains.