Treatment of Metastatic Urothelial Carcinoma with Reduced eGFR or Poor Performance Status
This protocol addresses first-line management of metastatic or unresectable urothelial carcinoma in patients who are not eligible for combination chemotherapy — due to impaired renal function (reduced eGFR) or reduced performance status — and whose tumours demonstrate high PD-L1 expression.
Patient Scenario
Patients qualify for this pathway when metastatic or unresectable urothelial carcinoma is confirmed and combination chemotherapy is contraindicated by at least one of:
- ECOG performance status greater than 2
- Glomerular filtration rate (eGFR) below 30 mL/min
- ECOG performance status of 2 combined with eGFR below 60 mL/min
Tumour tissue must also demonstrate high PD-L1 expression, confirmed by validated immunohistochemistry — defined by a combined positive score threshold for one agent, or by the proportion of tumour-infiltrating immune cells for the other.
Treatment Approach
Goal: Objective response
References
- Offer single agent CPI pembrolizumab or atezolizumab in case of high programmed death-ligand 1 (PDL-1) expression (for definitions see text).
- Patients are unfit for any platinum-based chemotherapy in case of PS > 2, GFR < 30 mL/min. or the combination of PS 2 and GFR < 60 mL/min.
- PD-L1 positivity for use of pembrolizumab is defined by immunohistochemistry as a CPS of ≥ 10 using the Dako 22C33 platform and, for atezolizumab, as positivity of ≥ 5% tumour-infiltrating immune cells using Ventana SP142.
- Pembrolizumab was tested in 370 patients with advanced UC or mUC ineligible for cisplatin, showing an ORR of 29% and CR in 7% of patients.
- Atezolizumab was evaluated in the same patient population in a phase II trial (n = 119) showing an ORR of 23% with 9% of patients achieving CR.