NECTIN4 Amplifications Predict Outcomes in Metastatic Urothelial Cancer

WEDNESDAY, May 8, 2024 (HealthDay News) -- For patients with metastatic urothelial cancer (mUC), NECTIN4 amplifications predict anti-NECTIN4 antibody-drug conjugate enfortumab vedotin (EV) response and outcomes, according to a study published online April 24 in the Journal of Clinical Oncology.

Niklas Klumper, M.D., from University Hospital Bonn in Germany, and colleagues examined the predictive value of NECTIN4 copy number variations (CNVs) in a multicenter EV-treated mUC patient cohort (108 patients). The correlations between CNVs with membranous NECTIN4 protein expression, EV treatment responses, and outcomes were examined. In addition, the prognostic value of NECTIN4 CNVs was measured in metastatic biopsies of 103 patients with non-EV-treated mUC. The Cancer Genome Atlas (TCGA) datasets, with 10,712 patients across 32 cancer types, were also queried for NECTIN4 CNVs.

NECTIN4 amplifications were frequent genomic events in muscle-invasive bladder cancer in TCGA and mUC cohorts (about 17 and 26 percent, respectively). The researchers found that NECTIN4 amplification represented a stable genomic alteration during metastatic progression in mUC-EV and was associated with enhanced membranous NECTIN4 protein expression. Overall, 96 and 32 percent of the 28 patients with NECTIN4 amplifications and the 74 nonamplified patients, respectively, demonstrated objective responses to EV. NECTIN4 amplifications led to a significant risk reduction for death in a multivariable adjusted Cox analysis (hazard ratio, 0.08). NECTIN4 amplifications occur frequently in other cancers based on analysis of the TCGA datasets.

"The frequent occurrence of NECTIN4 amplifications in other cancer types suggests that this biomarker is a promising candidate with broader applicability for clinical development of NECTIN4-targeted antibody-drug conjugates in a tumor-agnostic context," the authors write.

Several authors disclosed ties to pharmaceutical companies, including Astellas and Seagen, which manufacture enfortumab vedotin.

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