[NECTIN4 amplification as a predictive biomarker for enfortumab vedotin response]

Area of Science:

• Oncology
• Genetics
• Pharmacology

Background:

• Enfortumab vedotin (EV) is an antibody-drug conjugate targeting NECTIN4 for metastatic urothelial carcinoma (mUC).
• Patient response to EV varies, indicating a need for predictive biomarkers.
• Current treatment guidelines for mUC involve platinum-based chemotherapy and immune checkpoint inhibitors.

Purpose of the Study:

• To identify NECTIN4 amplification as a predictive biomarker for enfortumab vedotin (EV) efficacy in metastatic urothelial carcinoma (mUC).
• To assess the correlation between NECTIN4 amplification, protein expression, and clinical outcomes in mUC patients treated with EV.

Main Methods:

• Multicenter study analyzing 108 EV-treated mUC patients.
• Genomic NECTIN4 amplification assessed using fluorescence in situ hybridization (FISH).
• Correlation analysis between NECTIN4 amplification, membranous protein expression, objective response rate (ORR), and overall survival (OS).

Main Results:

• NECTIN4 amplification was found in approximately 25% of mUC tumors.
• NECTIN4 amplification strongly correlated with increased membranous NECTIN4 protein expression.
• Patients with NECTIN4-amplified tumors achieved a 96% objective response rate and had significantly prolonged overall survival.
• NECTIN4 amplification showed no prognostic impact in a control cohort without EV treatment.

Conclusions:

• NECTIN4 amplification serves as a stable and predictive biomarker for enfortumab vedotin (EV) treatment in metastatic urothelial carcinoma (mUC).
• NECTIN4 amplification can guide clinical treatment decisions for mUC patients.
• Potential cross-entity relevance of NECTIN4 amplification suggests further exploration of EV in other solid tumors.