Advanced Urothelial Carcinoma: Systemic Therapy

Advanced Urothelial Carcinoma: overview

This algorithm addresses systemic therapy for advanced urothelial carcinoma by line of therapy. In the first-line setting, the preferred regimen is enfortumab vedotin plus pembrolizumab (EV-302). When platinum chemotherapy is used instead, the chart separates cisplatin-fit patients, who receive cisplatin-based chemotherapy, from cisplatin-ineligible patients, who receive carboplatin-based chemotherapy. In both groups chemotherapy is followed by maintenance avelumab (JAVELIN Bladder 100).

Later-line options include single-agent enfortumab vedotin (EV-301), erdafitinib for FGFR3-altered tumors (THOR), sacituzumab govitecan (TROPHY-U-01) and pembrolizumab (KEYNOTE-045). The site's THOR summary reports an overall survival benefit for erdafitinib over chemotherapy in FGFR2/3-altered disease after prior platinum and immunotherapy (HR 0.64), establishing it as the standard for that population. TROPHY-U-01 showed an objective response rate of about 27% with sacituzumab govitecan in heavily pretreated disease after platinum and immunotherapy, establishing Trop-2 as a therapeutic target in urothelial carcinoma.

Trials behind this algorithm

• EV-302/KEYNOTE-A39 Powles T et al, NEJM, 2024; PMID: 38446675
• JAVELIN Bladder 100 Trial Powles T et al, NEJM, 2020, PMID: 32945632
• THOR Loriot Y et al, NEJM, 2023; PMID: 37870920
• TROPHY-U-01 Tagawa ST et al, JCO, 2021; PMID: 33929895
• Keynote 045 Bellmunt J et al, NEJM, 2017, PMID: 28212060

Background reading: Bladder Cancer board review notes.