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精确药物的瘤特异性活性在NCI-MATCH试验中

Ivvone Zhou¹, Deborah Plana^2,3, Adam C Palmer¹

¹Department of Pharmacology, Computational Medicine Program, UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Clinical cancer research : an official journal of the American Association for Cancer Research

|December 18, 2023

概括

精确的癌症治疗试验,如NCI-MATCH,可以揭示瘤特异性药物活性. 通过分析国家癌症研究所治疗选择分子分析 (NCI-MATCH) 数据,确定了对向疗法敏感的特定癌症类型,即使对所有瘤都不有效.

科学领域:

在瘤学瘤学.
遗传学是一个遗传学.
临床试验临床试验

背景情况:

美国国家癌症研究所分子分析治疗选择 (NCI-MATCH) 试验通过将向疗法与瘤的基因变化相匹配来研究精准医学,无论癌症类型如何.
大多数NCI-MATCH子协议的初步分析显示,在所有纳入的癌症类型中,瘤缩率有限.
形成了一个假设,这些精确的癌症疗法的疗效可能是特定于某些瘤类型的,类似于传统的癌症治疗.

研究的目的:

测试特定瘤类型对特定向疗法的敏感性差异的假设.
重新评估来自NCI-MATCH子协议的数据,以确定瘤特异性药物疗效信号.

主要方法:

变测试适用于10个NCI-MATCH子协议的瘤体积变化和无进展生存数据,包括435名患者.
统计学意义被评估,控制虚假发现率 (FDR) 使用本雅米尼-霍赫伯格程序.

主要成果:

在10个子协议中,有6个显示出具有统计学意义的瘤特异性药物敏感性的证据.
根据总体应答率,四种子方案以前被认为是无效的,在重新分析时显示出显著的瘤特异性活性.
关键发现包括FGFR氨酸激酶抑制剂在FGFR异常的泌尿腺癌和MEK抑制剂在BRAF非V600E突变的肺癌中的潜在疗效.
具有BRAF V600E突变的低度严重卵巢癌对BRAF和MEK联合抑制 (达布拉费尼布加上特拉美替尼布) 具有很高的敏感性.

结论:

这项研究证实了篮子试验在精密瘤学的实用性.
即使没有瘤不可知效应,篮子试验也可以揭示有价值的瘤特异性治疗活动,以便进一步研究.
这些发现支持癌症治疗的有针对性的方法,强调考虑瘤特异性反应的重要性.

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