First-Line Treatment of Metastatic or Unresectable Urothelial Carcinoma with Adequate Renal Function (eGFR ≥ 30 mL/min) and ECOG PS 0–2
Clinical Scenario
This protocol addresses patients with metastatic or unresectable urothelial carcinoma who are fit for combination therapy: ECOG performance status 0–2, glomerular filtration rate of at least 30 mL/min, and adequate organ functions confirming eligibility.
Eligibility Criteria
eGFR ≥ 30 mL/min
ECOG PS 0–2
Adequate organ function
- Metastatic or unresectable urothelial carcinoma
- ECOG performance status 0–2 (fit for combination therapy)
- Glomerular filtration rate ≥ 30 mL/min — the critical renal threshold for eligibility
- Adequate organ functions meeting treatment criteria
Treatment Approach
For patients meeting these criteria, current first-line management involves a combination of an antibody-drug conjugate and a checkpoint inhibitor, continued until disease progression. This combination represents the current standard of care for fit patients — the complete regimen, sequence, and stopping rules are detailed in the full protocol.
Clinical Goals
The primary objectives are objective response and complete response.
References
- Major criteria include ECOG PS 0-2, GFR ≥ 30mL/min. and adequate organ functions based on eligibility for treatment with EV + P.
- The combination of EV + P represents the new standard of care for patients who are deemed fit for combination therapies.
- Use antibody-drug conjugate enfortumab vedotin (EV) in combination with checkpoint inhibitor (CPI) pembrolizumab.
- This is based on EV-302/KEYNOTE 39A, a phase III trial that tested the antibody-drug conjugate EV directed against nectin-4 (EV: administered any number of times until progression) in combination with the immune CPI pembrolizumab (maximum of 35 cycles), against platinum-based chemotherapy.
- The overall ORR was 67.7% (29.1% CR) compared to 44.4% (12.5% CR) with platinum-based chemotherapy.
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