[Search for the T790M mutation: The need to persevere]

Rev Mal Respir. 2018 Sep;35(7):731-737. doi: 10.1016/j.rmr.2017.09.011. Epub 2018 Aug 14.
[Article in French]

Abstract

In cases of advanced EGFR mutation-positive non-small cell lung cancer, first or second generation EGFR-tyrosine kinase inhibitors (TKI-EGFR 1G or TKI-EGFR 2G) are recommended as first line treatment. Inexorably, progressive disease occurs and, in 50-60% of the cases, is secondary to a T790M resistant mutation. The prescription of osimertinib (TKI-EGFR3G) in second line is dependent on identification of the T790M mutation. We report 7 cases in which the identification of the T790M mutation required repeated analyses of cell free DNA and/or biopsies over a period of time. In some cases, a positive result was obtained a long time after progressive disease had been diagnosed during treatment with first or second generation EGFR-TKI. We discuss here the different modalities of screening for the T790M mutation and we encourage persevering in this search when no alternative mechanism of resistance has been identified.

Keywords: Adenocarcinoma; Adénocarcinome; Cancer bronchique non à petites cellules; EGFR receptor; Mutation T790M; Non-small cell lung cancer; Osimertinib; Récepteur à l’EGF; T790M mutation.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Amino Acid Substitution
  • Biopsy
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • DNA Mutational Analysis*
  • Drug Resistance, Neoplasm / genetics*
  • ErbB Receptors / genetics
  • Female
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Male
  • Methionine / genetics
  • Middle Aged
  • Mutation, Missense*
  • Protein Kinase Inhibitors / therapeutic use
  • Threonine / genetics
  • Time Factors

Substances

  • Protein Kinase Inhibitors
  • Threonine
  • Methionine
  • EGFR protein, human
  • ErbB Receptors