The National Lung Matrix Trial of personalized therapy in lung cancer

Nature. 2020 Jul;583(7818):807-812. doi: 10.1038/s41586-020-2481-8. Epub 2020 Jul 15.


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 smoke1-3. 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.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bayes Theorem
  • Carcinoma, Non-Small-Cell Lung / etiology
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Clinical Protocols
  • Clinical Trials as Topic
  • Cohort Studies
  • Genetic Markers*
  • Genotype
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Lung Neoplasms / etiology
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / therapy*
  • Molecular Targeted Therapy*
  • Oncogenes / genetics
  • Patient Selection
  • Precision Medicine*
  • Smoke / adverse effects
  • Smoking / genetics*
  • Triage


  • Genetic Markers
  • Smoke