Effective assessment of low times MET amplification in pleural effusion after epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) acquired resistance: Cases report

Medicine (Baltimore). 2018 Jan;97(1):e9021. doi: 10.1097/MD.0000000000009021.

Abstract

Rationale: The mechanism of the first-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) acquired resistance included T790M mutation, cellular-mesenchymal to epithelial transition factor (MET) or EGFR amplification, PIK3CA mutation, and transformation to small cell lung cancer. MET amplification accounted for only about 5% of the resistance cases.

Patients concerns: Few report detected MET amplification in pleural effusion. Here, we reported 2 lung adenocarcinoma cases with MET amplification in pleural effusion rapidly responded to crizotinib after EGFR-TKIs acquired resistance.

Diagnoses: Biopsy via bronchoscopy, next-generation sequencing (NGS) in pleural effusion.

Interventions: EGFR-TKIs (Icotinib), MET inhibitor crizotinib.

Outcomes: After a progression-free survival of 9 months and 23months, respectively, both cases progressed accompanying with pleural effusion. Results of NGS in pleural effusion showed MET amplification (2-3 times) in both cases. The 2 patients were treated with a MET inhibitor crizotinib and rapidly responded.

Conclusion: MET amplification in pleural effusion could predict a perfect response to crizotinib after EGFR-TKIs acquired resistance, even only a low times gene amplification.

Publication types

  • Case Reports

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / genetics*
  • Aged
  • Crizotinib
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Gene Amplification
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Male
  • Middle Aged
  • Pleural Effusion, Malignant / metabolism*
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins c-met / genetics*
  • Proto-Oncogene Proteins c-met / metabolism
  • Pyrazoles / therapeutic use
  • Pyridines / therapeutic use

Substances

  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyridines
  • Crizotinib
  • MET protein, human
  • Proto-Oncogene Proteins c-met