[3rd generation's TKI in lung cancer non-small cell EGFR-mutated having acquired a secondary T790M resistance]

Bull Cancer. 2015 Sep;102(9):749-57. doi: 10.1016/j.bulcan.2015.05.001. Epub 2015 Jul 30.
[Article in French]

Abstract

Activating EGFR mutations discovery and efficacy of 1st generation tyrosine kinase inhibitors (TKI), such as erlotinib or gefitinib, inaugurated the beginning of personalized medicine in the treatment of EGFR-mutated non-small cell lung cancer (NSCLC). However, all patients showed a tumor progression of 10 to 16 months after the onset of TKI therapy related to molecular resistance mechanisms as T790M mutation. Till now, patients suffering from EGFR-mutated NSCLC with acquired resistance have conventional treatment options. Two new 3rd generations' TKI, AZD9291 and rociletinib, are currently being studied in phases 1-3 studies. Preliminary results show relevant therapeutic properties in patients with T790M mutated-EGFR NSCLC. This review aims to highlight these new molecules, their effectiveness and their clinical toxicities in the treatment of advanced stages of NSCLC expressing the T790M mutation.

Keywords: AZD9291; Cancer bronchique non à petites cellules; EGFR mutation; Mutation EGFR; Mutation T790M; Non-small cell lung cancer; Rociletinib; Rocilétinib; T790M mutation.

Publication types

  • Review

MeSH terms

  • Acrylamides / therapeutic use*
  • Aniline Compounds / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Disease Progression
  • Drug Resistance, Neoplasm / genetics*
  • ErbB Receptors / genetics*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Mutation*
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrimidines / therapeutic use*

Substances

  • Acrylamides
  • Aniline Compounds
  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Pyrimidines
  • osimertinib
  • rociletinib
  • ErbB Receptors