PTEN, ATM, IDH1 mutations and MAPK pathway activation as modulators of PFS and OS in patients treated by first line EGFR TKI, an ancillary study of the French Cooperative Thoracic Intergroup (IFCT) Biomarkers France project

Lung Cancer. 2021 Jan;151:69-75. doi: 10.1016/j.lungcan.2020.11.008. Epub 2020 Nov 13.

Abstract

Objectives: Tumor mutation screening is standard of care for patients with stage IV NSCLC. Since a couple of years, widespread NGS approaches used in routine diagnostics to detect driver mutations such as EGFR, KRAS, BRAF or MET allows the identification of other alterations that could modulated the intensity or duration of response to targeted therapies. The prevalence of co-occurring alterations that could affect response or prognosis as not been largely analyzed in clinical settings and large cohorts of patients. Thanks to the IFCT program "Biomarkers France", a collection of samples and data at a nation-wide level was available to test the impact of co-mutations on first line EGFR TKI in patients with EGFR mutated cancers.

Materials and methods: Targeted NGS was assessed on available (n = 208) samples using the Ion AmpliSeq™ Cancer Hotspot Panel v2 to screen for mutations in 50 different cancer genes.

Results: This study showed that PTEN inactivating mutations, ATM alterations, IDH1 mutations and complex EGFR mutations were predictors of short PFS in patients with a stage 4 lung adenocarcinoma receiving first line EGFR TKI and that PTEN, ATM, IDH1 and KRAS mutations as well as alterations in the MAPK pathway were related to shorter OS.

Conclusion: These findings may lead to new treatment options in patients with unfavorable genotypes to optimize first line responses.

Keywords: EGFR mutations; Molecular profiles; Next-generation sequencing; Non-small cell lung cancer; Prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ataxia Telangiectasia Mutated Proteins
  • Biomarkers
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • ErbB Receptors / genetics
  • France / epidemiology
  • Humans
  • Isocitrate Dehydrogenase
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Mutation
  • PTEN Phosphohydrolase
  • Protein Kinase Inhibitors* / therapeutic use

Substances

  • Biomarkers
  • Protein Kinase Inhibitors
  • Isocitrate Dehydrogenase
  • IDH1 protein, human
  • EGFR protein, human
  • ErbB Receptors
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • PTEN Phosphohydrolase
  • PTEN protein, human