An international survey highlights how clinicians assess patient suitability for the first-line combination of enfortumab vedotin and pembrolizumab (EV-P) in advanced urothelial malignancies.

Urothelial carcinoma accounts for 90% of bladder cancers. EV-P has shown superior efficacy over platinum-based chemotherapy and is now a standard first-line treatment option in advanced disease. However, the unique toxicity profile of EV-P raises questions about patient selection, particularly outside specialist centres.

A survey led by researchers from Spain, the US and the UK aimed to capture real-world perspectives on eligibility criteria, contraindications and barriers to EV-P use in daily practice.

Between February and March 2025, 201 genitourinary clinicians from 32 countries completed a 17-question online survey. Most respondents (90%) worked in academic institutions and had extensive experience managing advanced urothelial carcinoma.

EV-P and urothelial cancer

The results, published in the journal The Oncologist, showed grade ≥2 neuropathy (64.2%), Eastern Cooperative Oncology Group performance status ≥3 (59.2%), and non-urothelial histology >50% (59.2%) as the most frequently cited absolute contraindications to EV-P from the respondents.

Other key concerns included severe ocular abnormalities, HbA1c >11%, significant dermatological comorbidities, liver impairment grade ≥2 and dependence on dialysis. These factors align closely with exclusion criteria from the pivotal EV-302 trial published in 2024.

While cost was a significant barrier for 59% of clinician respondents, most agreed that consensus guidance would help non-specialist oncologists select appropriate candidates for EV-P treatment. The majority did not consider age alone as a limiting factor.

For patients deemed ineligible for EV-P, platinum-based chemotherapy followed by maintenance avelumab was the preferred alternative (53.2%). Other alternatives were nivolumab-gemcitabine-cisplatin (13.4%), carboplatin-gemcitabine only (11.4%) and a PD-1 protein/PD-1 ligand regimen (10.4%).

Limitations and future directions

The researchers acknowledged several limitations, including potential selection bias towards academic rather than community-based hospital clinicians, who only made up 10% of respondents; some geographical under-representation, particularly from certain regions in the US and Australia; and minimal or no hands-on exposure to the EV-P regimen outside of clinical trial settings. The findings may therefore reflect expert perceptions rather than real-world outcomes, they said.

Nevertheless, the need to generate real-world evidence and integrate biomarker-based tools with clinical judgment in refining patient selection was evident, the researchers concluded.

This study underscores the importance of clinical vigilance, proactive toxicity management and tailored guidance to ensure the safe integration of EV-P into everyday clinical practice.

Reference
Grande E et al. Guiding First-Line Treatment Decisions in Advanced Urothelial Carcinoma: A Global Survey. The Oncologist 2025; 6 Oct:doi.org/10.1093/oncolo/oyaf333.