WEDNESDAY, May 8, 2024 -- 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).

2024年5月8日，星期三——根据4月24日在线发表在《临床肿瘤学杂志》上的一项研究，对于转移性尿路上皮癌（mUC）患者，NECTIN4扩增可预测抗NECTIN4抗体-药物偶联物enfortumab vedotin（EV）的反应和结果。来自德国波恩大学医院的医学博士Niklas Klumper及其同事研究了多中心EV治疗的mUC患者队列（108名患者）中NECTIN4拷贝数变异（CNV）的预测价值。

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).

检查了CNV与膜NECTIN4蛋白表达，EV治疗反应和结局之间的相关性。此外，在103例非EV治疗的mUC患者的转移活检中测量了NECTIN4 CNV的预后价值。还查询了32种癌症类型的10712名患者的癌症基因组图谱（TCGA）数据集的NECTIN4 CNV。NECTIN4扩增是TCGA和mUC队列中肌肉浸润性膀胱癌的常见基因组事件（分别约为17%和26%）。

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.

研究人员发现，NECTIN4扩增代表了mUC EV转移过程中稳定的基因组改变，并与增强的膜NECTIN4蛋白表达有关。总体而言，在28例NECTIN4扩增患者和74例非扩增患者中，分别有96%和32%表现出对EV的客观反应。

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-ta.

在多变量调整后的Cox分析中，NECTIN4扩增导致死亡风险显着降低（风险比为0.08）。根据对TCGA数据集的分析，NECTIN4扩增在其他癌症中经常发生。”NECTIN4扩增在其他癌症类型中的频繁发生表明，该生物标志物是一种有前途的候选物，对NECTIN4 ta的临床开发具有更广泛的适用性。