Enfortumab Vedotin and Pembrolizumab in Metastatic Urothelial Cancer

Evidence Supporting No PD-L1 Testing Requirement

• The European Association of Urology guidelines (2025) recommend enfortumab vedotin plus pembrolizumab as the new standard of care for patients eligible for combination therapy, with no mention of PD-L1 testing requirement 3
• The European Society for Medical Oncology (ESMO) clinical practice guidelines also recommend enfortumab vedotin plus pembrolizumab without requiring PD-L1 testing 4
• The EV-302 trial showed that enfortumab vedotin plus pembrolizumab demonstrated superior overall survival (OS) of 31.5 months versus 16.1 months with platinum-based chemotherapy (HR 0.47), without patient selection based on PD-L1 status 1, 2

Clinical Efficacy of EV Plus Pembrolizumab

• The EV-302 trial demonstrated an objective response rate of 67.7% (29.1% complete response) versus 44.4% (12.5% complete response) with platinum-based chemotherapy 3
• The EV-302 trial demonstrated a median progression-free survival of 12.5 versus 6.3 months (HR 0.45) 3
• The EV-302 trial demonstrated a median overall survival of 31.5 versus 16.1 months (HR 0.47) 1, 2

Safety Considerations

• The key enfortumab vedotin toxicities include rash, neuropathy, ocular disorders, and hyperglycemia 3

Clinical Algorithm for Treatment Selection

• The European Association of Urology recommends enfortumab vedotin plus pembrolizumab as the preferred first-line option for patients eligible for combination therapy, with no PD-L1 testing required 3
• If the patient is not eligible for enfortumab vedotin or it is not available, consider platinum/gemcitabine plus atezolizumab or pembrolizumab for PD-L1 positive patients, with PD-L1 testing required in this scenario 3