Systemic therapy for urothelial cancer: platinum defeated?

Abstract Platinum-based chemotherapy was the mainstay of treatment for advanced urothelial carcinoma (UC) for decades, but the therapeutic landscape has fundamentally changed. Immune checkpoint blockade showed overall survival (OS) benefit in phase 3 trials: as second line (pembrolizumab), as maintenance therapy (avelumab) following frontline chemotherapy response, or in combination with cisplatin-chemotherapy (nivolumab). Options after failure to chemo- and immunotherapy consist of enfortumab vedotin (EV) or erdafitinib (in case of FGFR3 mutations). However, the most significant change was the superiority of EV plus pembrolizumab over chemotherapy in the EV302 trial, which has become the new standard frontline therapy. In the peri-operative setting, anti-PD-(L)1 has shown benefit as adjuvant therapy (nivolumab and pembrolizumab; not yet for OS) and in the peri-operative setting, combined with chemotherapy (durvalumab; including OS).