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    The National Lung Matrix Trial of personalized therapy in lung cancer

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    Authors
    Middleton, G.
    Fletcher, P.
    Popat, S.
    Savage, J.
    Summers, Yvonne J
    Greystoke, A.
    Gilligan, D.
    Cave, J.
    O'Rourke, N.
    Brewster, A.
    Toy, E.
    Spicer, J.
    Jain, P.
    Dangoor, A.
    Mackean, M.
    Forster, M.
    Farley, A.
    Wherton, D.
    Mehmi, M.
    Sharpe, R.
    Mills, T. C.
    Cerone, M. A.
    Yap, T. A.
    Watkins, T. B. K.
    Lim, E.
    Swanton, C.
    Billingham, L.
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    Affiliation
    Institute of Immunology & Immunotherapy, University of Birmingham, Birmingham, UK.
    Issue Date
    2020
    
    Metadata
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    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 smoke1-3. 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.
    Citation
    Middleton G, Fletcher P, Popat S, Savage J, Summers Y, Greystoke A, et al. The National Lung Matrix Trial of personalized therapy in lung cancer. Nature. 2020;583(7818):807-12.
    Journal
    Nature
    URI
    http://hdl.handle.net/10541/623186
    DOI
    10.1038/s41586-020-2481-8
    PubMed ID
    32669708
    Additional Links
    https://dx.doi.org/10.1038/s41586-020-2481-8
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41586-020-2481-8
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