The National Lung Matrix Trial of personalized therapy in lung cancer
The National Lung Matrix Trial of personalized therapy in lung cancer
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DOI：
10.1038/s41586-020-2481-8
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发表时间：
2020-07-15
期刊：
影响因子：
64.8
通讯作者：
Billingham, Lucinda
中科院分区：
文献类型：
--
作者：
Middleton, Gary;Fletcher, Peter;Billingham, Lucinda
大多数针对非小细胞肺癌(NSCLC)的靶向治疗针对的是致癌驱动因素，这些驱动因素在暴露于烟草烟雾的患者中更为普遍(1-3)。由于这一群体约占所有肺癌患者的20%，发现与烟草相关的非小细胞肺癌分层药物选择是当务之急。伞形试验寻求通过筛查肿瘤的多种基因组改变并将患者分流到几种基因匹配的治疗药物中的一种，来简化基于基因的治疗的研究。在这里，我们报告了正在进行的国家肺基质试验的19个药物生物标记物队列的当前结果，这是非小细胞肺癌中最大的伞形试验。我们使用下一代测序来根据患者的肿瘤基因型别将患者与适当的靶向治疗相匹配。贝叶斯试验设计使来自仍在招募的开放队列的结果数据能够与来自封闭队列的数据一起报告。在接受筛查的5467名患者中，有2,007名在分子上符合进入试验的条件，302名进入试验接受基因匹配治疗-其中14人重新注册进入试验，接受序贯试验药物。尽管临床前数据支持药物-生物标记物组合，但目前的证据显示，有限数量的组合显示出临床相关的益处，这些组合仍然集中在与吸烟最少相关的肺癌患者中。目前的结果来自正在进行的国家肺基质试验，这是一项治疗非小细胞肺癌的伞形试验，根据患者的肿瘤基因型进行分类，并与靶向治疗药物匹配。
The majority of targeted therapies for non-small-cell lung cancer (NSCLC) are directed against oncogenic drivers that are more prevalent in patients with light exposure to tobacco smoke(1-3). As this group represents around 20% of all patients with lung cancer, the discovery of stratified medicine options for tobacco-associated NSCLC is a high priority. Umbrella trials seek to streamline the investigation of genotype-based treatments by screening tumours for multiple genomic alterations and triaging patients to one of several genotype-matched therapeutic agents. Here we report the current outcomes of 19 drug-biomarker cohorts from the ongoing National Lung Matrix Trial, the largest umbrella trial in NSCLC. We use next-generation sequencing to match patients to appropriate targeted therapies on the basis of their tumour genotype. The Bayesian trial design enables outcome data from open cohorts that are still recruiting to be reported alongside data from closed cohorts. Of the 5,467 patients that were screened, 2,007 were molecularly eligible for entry into the trial, and 302 entered the trial to receive genotype-matched therapy-including 14 that re-registered to the trial for a sequential trial drug. Despite pre-clinical data supporting the drug-biomarker combinations, current evidence shows that a limited number of combinations demonstrate clinically relevant benefits, which remain concentrated in patients with lung cancers that are associated with minimal exposure to tobacco smoke.Current outcomes are reported from the ongoing National Lung Matrix Trial, an umbrella trial for the treatment of non-small-cell lung cancer in which patients are triaged according to their tumour genotype and matched with targeted therapeutic agents.