[Paradigm shift in systemic therapy for metastatic urothelial carcinoma-antibody-drug conjugates (ADCs) and fibroblast growth factor receptor (FGFR) inhibitors].

Background: Patients with locally advanced or metastatic urothelial carcinoma face a poor prognosis. Standard first-line treatment involves platinum-based combinations followed by avelumab maintenance therapy. Follow-up therapies include enfortumab vedotin, vinflunine, and taxanes.

Objective: To analyze new drug combinations in first-line and follow-up treatment for metastatic urothelial carcinoma concerning their clinical relevance, toxicities, and novel treatment sequences.

Materials and methods: Analysis of new study data from EV-302/KN-A39 (enfortumab vedotin and pembrolizumab) and CheckMate-901 (nivolumab and gemcitabine-cisplatin) for untreated metastatic patients as well as TROPHY-U-01 (sacituzumab govitecan) and THOR (erdafitinib) for later lines.

Results: The new standard in first-line treatment for metastatic urothelial carcinoma is the combination of enfortumab vedotin and pembrolizumab. For cisplatin-eligible patients with contraindications to enfortumab vedotin, the combination of nivolumab and gemcitabine-cisplatin offers an alternative. Erdafitinib presents a new biomarker-based option in the follow-up treatment of metastatic urothelial carcinoma.

Conclusion: These novel combinations are revolutionizing the treatment standard for metastatic urothelial carcinoma and necessitate a new approach to managing side effects.