title: High MET amplification level as a resistance mechanism to osimertinib (AZD9291) in a patient that symptomatically responded to crizotinib treatment post-osimertinib progression.
abstract: Third-generation EGFR TKI has been approved in the US and EU for the treatment of EGFR mutant T790M+ NSCLC patients that are resistant to first- or second generation EGFR TKIs. Here we report a patient who developed resistance to osimertinib after a confirmed partial response for 9 months. Pre-osimertinib and post-osimertinib tumor biopsy revealed the emergence of high level of MET amplification (30 copies) post osimertinib treatment. Patient was treated with single agent crizotinib, a known MET inhibitor, with transient symptomatic benefit. MET amplification is one potential resistance mechanism to osimertinib and combination of osimertinib and a MET inhibitor should be investigated post-osimertinib progression in EGFR mutant T790M+ NSCLC patients whose harbored acquired MET amplification.
authors.affiliation: Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, Orange, CA 92868, USA. Electronic address: Ignatius.ou@uci.edu.
authors.forename: Sai-Hong Ignatius
authors.initials: SI
authors.lastname: Ou
authors.affiliation: Foundation Medicine, Inc., Cambridge, MA 02141, USA.
authors.forename: Nikita
authors.initials: N
authors.lastname: Agarwal
authors.affiliation: Foundation Medicine, Inc., Cambridge, MA 02141, USA.
authors.forename: Siraj M
authors.initials: SM
authors.lastname: Ali
mesh_terms: D000178:Acrylamides / Q000494:pharmacology* / Q000627:therapeutic use; D000368:Aged; D000814:Aniline Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D000077547:Crizotinib; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D057915:Drug Substitution; D017809:Fatal Outcome; D005260:Female; D005784:Gene Amplification; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics*; D011720:Pyrazoles / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D019233:Retreatment; D014057:Tomography, X-Ray Computed; D007211:Indoles; D011743:Pyrimidines
chemical_list: D000178:Acrylamides; D000814:Aniline Compounds; D000077547:Crizotinib; D047428:Protein Kinase Inhibitors; D019859:Proto-Oncogene Proteins c-met; D011720:Pyrazoles; D011725:Pyridines; C000596361:osimertinib; D007211:Indoles; D011743:Pyrimidines
keywords: Acquired resistance; METamplification; Non-small-cell lung cancer; Osimertinib; Third-generation EGFR TKI