Metastatic or Unresectable Urothelial Carcinoma with eGFR >50 mL/min and Contraindications to Enfortumab Vedotin — Cisplatin-Eligible
This protocol addresses patients with metastatic or unresectable urothelial carcinoma (ECOG performance status 0–1, eGFR >50 mL/min) who are eligible for cisplatin-based chemotherapy but have contraindications to enfortumab vedotin, or for whom enfortumab vedotin is not available.
Clinical Scenario
- Metastatic or unresectable urothelial carcinoma
- ECOG performance status 0–1
- Glomerular filtration rate (eGFR) >50 mL/min
- Contraindications to enfortumab vedotin, or enfortumab vedotin not available
- Eligible for cisplatin-based chemotherapy
Treatment Approach
In this setting, the protocol includes biomarker-directed therapy guided by molecular testing results — the choice of agent depends on specific findings identified at workup.
Full regimen, decision criteria, and sequencing are in the structured protocol below.
References
- If contraindications for EV (or EV not available) and cisplatin-eligible: Offer cisplatin/gemcitabine in combination with CPI nivolumab.
- If contraindications for EV or EV not available: Offer platinum-containing combination chemotherapy (cisplatin or carboplatin plus gemcitabine) followed by maintenance treatment with CPI avelumab in patients with at least stable disease on chemotherapy.
- Some patients might not be eligible for or refuse treatment with EV, including patients with uncontrolled diabetes, peripheral neuropathy grade ≥2 and pre-existing significant skin disorders.
- Offer antibody-drug conjugate Trastuzumab deruxtecan in case of human epidermal growth factor receptor (HER) 2 over expression (IHC 3+) and consider in case of HER2 (IHC 2+).
- If actionable FGFR alterations: offer erdafitinib.
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