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.

中文翻译：

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肺癌个体化治疗的全国肺基质试验

非小细胞肺癌 (NSCLC) 的大多数靶向治疗都是针对致癌驱动因素，这些驱动因素在轻度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%，因此发现烟草相关 NSCLC 的分层药物选择是当务之急。伞式试验旨在通过筛选肿瘤的多种基因组改变并将患者分类为几种基因型匹配的治疗药物之一来简化基于基因型治疗的研究。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-生物标志物队列的当前结果，该试验是 NSCLC 中最大的伞式试验。我们使用下一代测序根据患者的肿瘤基因型将患者匹配到适当的靶向治疗。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。在筛选的 5,467 名患者中，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型匹配治疗，其中 14 名重新注册参加试验以获得序贯试验药物。尽管临床前数据支持药物-生物标志物组合，但目前的证据表明，有限数量的组合显示出临床相关益处，这些益处仍然集中在与烟草烟雾接触最少相关的肺癌患者身上。目前的结果来自正在进行的国家肺基质试验，