Prevalence of T790M mutation among TKI-therapy resistant Lebanese lung cancer patients based on liquid biopsy analysis: a first report from a major tertiary care center

Mol Biol Rep. 2019 Aug;46(4):3671-3676. doi: 10.1007/s11033-019-04797-5. Epub 2019 May 30.

Abstract

Lung adenocarcinoma patients have variable prognosis due to many factors. Detection of epidermal growth factor receptor (EGFR) activating mutations is one of the factors that implies the need for initiating a first-line EGFR tyrosine kinase inhibitor (TKI) treatment. However, T790M resistance mutation emergence during treatment accounts for most EGFR-TKI drug resistance. The traditional sample taken for T790M mutation analysis is tissue biopsy, but its numerous disadvantages have introduced liquid biopsy as a preferred method for testing. We studied the prevalence of T790M mutation among pulmonary adenocarcinoma patients in Lebanese patients based on liquid biopsy testing the circulating tumor DNA (ctDNA). We have reviewed the laboratory charts of 52 patients who developed resistance on treatment and referred to AUBMC for EGFR T790M Liquid Biopsy to analyze the mutational analysis results for EGFR T790M. In total, 82.6% of the tested lung cancer patients were positive for a specific EGFR mutation. Among these patients, a total 26.9% were positive for T790M, which is comparable to the international prevalence of this mutation. However, for those cases who developed resistance with circulating DNA showing an EGFR mutation, 50% were positive for T790M that is also comparable to the international literature. This is the first report from Lebanon to discuss the prevalence of T790M mutation using liquid biopsy among Lebanese population. An important landmark molecular epidemiology study that will be a reference to all oncologists in Lebanon and the region in assessing the potential for targeted therapy options in the country. In addition, the data will be of an asset to the building international literature related to this disease.

Keywords: EGFR; Lebanese population; Liquid biopsy; T790M.

MeSH terms

  • Adenocarcinoma of Lung / drug therapy
  • Adenocarcinoma of Lung / genetics*
  • Adenocarcinoma of Lung / pathology
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • Circulating Tumor DNA / genetics
  • Drug Resistance, Neoplasm / genetics
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics*
  • Female
  • Humans
  • Lebanon
  • Liquid Biopsy
  • Lung / pathology
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Molecular Targeted Therapy
  • Mutation
  • Protein Kinase Inhibitors / therapeutic use*
  • Tertiary Care Centers

Substances

  • Antineoplastic Agents
  • Circulating Tumor DNA
  • Protein Kinase Inhibitors
  • ErbB Receptors