When single-agent PD-L1 immunotherapy does not achieve an objective response in patients with metastatic or unresectable urothelial carcinoma who were already ineligible for combination therapy, a defined next-line strategy applies. This page describes that specific clinical scenario and the framework for moving forward.
These patients have metastatic or unresectable urothelial carcinoma and were not eligible for combination therapy due to an ECOG performance status greater than 2, a glomerular filtration rate below 30 mL/min, or an ECOG performance status of 2 combined with a GFR below 60 mL/min. At first-line, they qualified on the basis of high PD-L1 expression — a combined positive score of 10 or above for pembrolizumab, or tumour-infiltrating immune cells of 5% or above for atezolizumab.
The prior line consisted of single-agent pembrolizumab (combined positive score ≥ 10) or atezolizumab (tumour-infiltrating immune cells ≥ 5%). This protocol is indicated when that immunotherapy did not achieve an objective response — the defined escalation trigger for this population.
Following immunotherapy failure in this setting, treatment selection is guided by the individual tumour's biomarker profile. Antibody-drug conjugate therapy is central to the approach, and additional targeted or chemotherapy options may apply depending on specific tumour characteristics. The complete selection algorithm and full options are detailed in the structured protocol.