High MET amplification level as a resistance mechanism to osimertinib (AZD9291) in a patient that symptomatically responded to crizotinib treatment post-osimertinib progression

Lung Cancer. 2016 Aug:98:59-61. doi: 10.1016/j.lungcan.2016.05.015. Epub 2016 May 25.

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.

Keywords: Acquired resistance; METamplification; Non-small-cell lung cancer; Osimertinib; Third-generation EGFR TKI.

Publication types

  • Case Reports

MeSH terms

  • Acrylamides / pharmacology*
  • Acrylamides / therapeutic use
  • Aged
  • Aniline Compounds / pharmacology*
  • Aniline Compounds / therapeutic use
  • Crizotinib
  • Disease Progression
  • Drug Resistance, Neoplasm / genetics*
  • Drug Substitution
  • Fatal Outcome
  • Female
  • Gene Amplification*
  • Humans
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics*
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins c-met / genetics*
  • Pyrazoles / therapeutic use*
  • Pyridines / therapeutic use*
  • Retreatment
  • Tomography, X-Ray Computed

Substances

  • Acrylamides
  • Aniline Compounds
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyridines
  • osimertinib
  • Crizotinib
  • Proto-Oncogene Proteins c-met