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Investigational New Drugs
Published in: Investigational New Drugs 3/2016

01-06-2016 | SHORT REPORT

A never-smoker lung adenocarcinoma patient with a MET exon 14 mutation (D1028N) and a rapid partial response after crizotinib

Authors: Linda Mahjoubi, Anas Gazzah, Benjamin Besse, Ludovic Lacroix, Jean-Charles Soria

Published in: Investigational New Drugs | Issue 3/2016

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Summary

During the past decade, the treatment of lung adenocarcinomas has been revolutionized with novel molecular targeted therapies. We describe a case of clinical activity of crizotinib in a female patient with a lung adenocarcinoma displaying a MET exon 14 donor splice site mutation (D1028N) detected using next generation sequencing. Within 5 weeks of crizotinib therapy, a partial response was observed in this 67 year-old woman. Further clinical trials of crizotinib are needed for non-small cell lung cancer exhibiting MET mutations.
Literature
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Cui JJ, Tran-Dube M, Shen H, Nambu M, Kung PP, Pairish M, et al. (2011) Structure based drug design of crizotinib (PF-02341066), a potent and selective dual inhibitor of mesenchymal-epithelial transition factor (c-MET) kinase and anaplastic lymphoma kinase (ALK). J Med Chem 18:6342–6363CrossRef
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Cancer Genome Atlas Research Network (2014) Comprehensive molecular profiling of lung adenocarcinoma. Nature 511:543–550CrossRef
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Frampton GM, Ali SM, Rosenzweig M, Chmielecki J, Lu X, Bauer TM, et al. (2015) Activation of MET via diverse exon 14 splicing alterations occurs in multiple tumor types and confers clinical sensitivity to MET inhibitors. Cancer Discov 8:850–859CrossRef
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Kong-Beltran M, Seshagiri S, Zha J, Zhu W, Bhawe K, Mendoza N, et al. (2006) Somatic mutations lead to an oncogenic deletion of met in lung cancer. Cancer Res 66(1):283–289CrossRefPubMed
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Camidge DR, Ou S, Shapiro G, Otterson GA, Villaruz LC, Villalona-Calero MA, et al (2014) Efficacy and safety of crizotinib in patients with advanced c-MET-amplified non-small cell lung cancer (NSCLC). J Clin Oncol 32:5. doi:10.​1200/​JCO.​2013.​49.​4757
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Jenkins RW, Oxnard GR, Elkin S, Sullivan EK, Carter JL, Barbie DA (2015) Response to Crizotinib in a Patient With Lung Adenocarcinoma Harboring a MET Splice Site Mutation. Clin Lung Cancer 5:e101–e104CrossRef
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Spigel DR, Edelman MJ, O’Byrne K, et al (2014) Onartuzumab plus erlotinib versus erlotinib in previously treated stage IIIb or IV NSCLC: Results from the pivotal phase III randomized, multicenter, placebo-controlled METLung (OAM4971g) global trial. J Clin Oncol 32(Suppl; abstr 8000):5s
Metadata
Title
A never-smoker lung adenocarcinoma patient with a MET exon 14 mutation (D1028N) and a rapid partial response after crizotinib
Authors
Linda Mahjoubi
Anas Gazzah
Benjamin Besse
Ludovic Lacroix
Jean-Charles Soria
Publication date
01-06-2016
Publisher
Springer US
Published in
Investigational New Drugs / Issue 3/2016
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI
https://doi.org/10.1007/s10637-016-0332-0

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