Metastatic Urothelial Carcinoma — FGFR2/3-Altered

Post-platinum sequencing for FGFR2/3-altered metastatic urothelial carcinoma: first-line enfortumab vedotin plus pembrolizumab (preferred) or platinum-based chemotherapy, then erdafitinib for the FGFR-altered subset after platinum exposure, then a remaining antibody-drug conjugate.

First-line systemic therapy selection

1L: Enfortumab vedotin + pembrolizumab

Preferred first line regardless of cisplatin eligibility; EV-302 showed superior overall survival versus platinum-based chemotherapy. Monitor for skin reactions, peripheral neuropathy, and hyperglycemia (enfortumab vedotin) and immune-related adverse events (pembrolizumab).

Evidence: EV-302

1L: Platinum-based chemotherapy (gemcitabine + cisplatin, or + carboplatin if cisplatin-ineligible)

Alternative first line when enfortumab vedotin + pembrolizumab is not feasible. Use carboplatin for cisplatin-ineligible patients (impaired renal function, ECOG 2, hearing loss, neuropathy); consider avelumab switch-maintenance in non-progressors.

2L: Platinum-based chemotherapy (gemcitabine + cisplatin or carboplatin)

For patients who received enfortumab vedotin + pembrolizumab first line: platinum-based chemotherapy is the standard next line and establishes the prior-platinum exposure required before erdafitinib.

2L: Erdafitinib (FGFR2/3-altered, post-platinum)

For the FGFR2/3-altered subset after platinum-based chemotherapy (platinum-first patients); THOR showed an overall survival benefit versus chemotherapy. Titrate dose by serum phosphate; mandatory ophthalmologic monitoring for central serous retinopathy, plus management of hyperphosphatemia, stomatitis, and nail/skin changes.

3L+: Erdafitinib (FGFR2/3-altered, post-platinum)

For the FGFR2/3-altered subset after enfortumab vedotin + pembrolizumab followed by platinum-based chemotherapy; same monitoring as post-platinum erdafitinib in earlier lines.

3L+: Remaining antibody-drug conjugate (sacituzumab govitecan, or enfortumab vedotin if not previously used)

After FGFR-directed therapy. Choose an antibody-drug conjugate not already used earlier in the sequence; consider a clinical trial where available.