英国伯明翰大学Gary Middleton研究组报告了肺癌个性化治疗的国家肺基质试验结果。相关论文发表在2020年7月15日出版的《自然》杂志上。
他们报告了正在进行的国家肺癌基质试验（非小细胞肺癌（NSCLC）中最大的总体试验）中19个药物-生物标志物队列的当前结果。他们使用二代测序技术，根据患者的肿瘤基因型将其与适当的靶向治疗相匹配。贝叶斯试验设计可以将仍在招募的开放队列的结果数据与封闭队列的数据一起进行报告。
在筛选出的5467名患者中，有2007名具有分子资格进入该试验，而302名进入该试验以接受基因型匹配疗法-包括14名重新注册为顺序试验药物的试验者。尽管临床前数据支持药物-生物标志物的组合，但目前的证据表明，有限的组合显示出与临床相关的益处，这仍然只对吸烟量最小相关的肺癌患者有益。
据了解，NSCLC的大多数靶向疗法针对的是致癌性驱动因素，在接触烟草烟雾的患者中更为普遍。由于该组约占所有肺癌患者的20％，因此烟草相关的NSCLC分层药物选择的发现已成当务之急。伞类试验旨在通过筛选肿瘤的多种基因组，改变并将患者分到几种基因型匹配的治疗药物之中，从而简化基于基因型的治疗研究。
附：英文原文
Title: The National Lung Matrix Trial of personalized therapy in lung cancer
Author: Gary Middleton, Peter Fletcher, Sanjay Popat, Joshua Savage, Yvonne Summers, Alastair Greystoke, David Gilligan, Judith Cave, Noelle ORourke, Alison Brewster, Elizabeth Toy, James Spicer, Pooja Jain, Adam Dangoor, Melanie Mackean, Martin Forster, Amanda Farley, Dee Wherton, Manita Mehmi, Rowena Sharpe, Tara C. Mills, Maria Antonietta Cerone, Timothy A. Yap, Thomas B. K. Watkins, Emilia Lim, Charles Swanton, Lucinda Billingham
Issue&Volume: 2020-07-15
Abstract: 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 smoke1,2,3. 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.
DOI: 10.1038/s41586-020-2481-8
Source: https://www.nature.com/articles/s41586-020-2481-8
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
