This protocol applies to patients with metastatic or unresectable urothelial carcinoma, ECOG performance status 0–1, and eGFR > 50 mL/min, who have progressed on first-line cisplatin-based chemotherapy combined with a checkpoint inhibitor, and for whom enfortumab vedotin is contraindicated or unavailable.
The patient is fit for cisplatin (ECOG 0–1, eGFR > 50 mL/min) but cannot receive enfortumab vedotin. Contraindications to enfortumab vedotin include conditions such as uncontrolled diabetes, peripheral neuropathy grade ≥ 2, or significant pre-existing skin disorders. This protocol specifically addresses next-step management in that population.
Patients in this scenario have previously received cisplatin/gemcitabine combined with nivolumab (followed by nivolumab maintenance until progression), or cisplatin/gemcitabine followed by maintenance avelumab in those with at least stable disease. This protocol defines the step taken when that first-line regimen failed to achieve an objective response.
Management in this setting involves systemic options selected based on molecular biomarker profiling and prior treatment history. The complete regimen, sequencing, and decision criteria are in the full protocol.
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.
If actionable FGFR alterations and prior CPI: offer erdafitinib.
If no prior CPI: offer pembrolizumab.
Consider single agent chemotherapy (docetaxel, paclitaxel, vinflunine).
View source ↗