[Oncogenic drivers in daily practice improve overall survival in patients with lung adenocarcinoma]

Rev Mal Respir. 2016 Nov;33(9):751-756. doi: 10.1016/j.rmr.2015.12.009. Epub 2016 Mar 24.
[Article in French]

Abstract

Background: EGFR tyrosine kinase inhibitors and crizotinib are nowadays the optimal treatment for metastatic lung cancer with activation of EGFR mutations and ALK rearrangement. In addition, several targeted agents are in development for lung cancer with other oncodrivers. In France, since 2011, six oncodrivers are routinely tested in patients with stage IV. The aim of this study was to assess whether systematic detection of oncodrivers and matched targeted therapy improve overall survival in patients with advanced lung adenocarcinoma.

Methods: This study included all consecutive patients treated in our department for advanced lung adenocarcinoma from January 2012 to December 2013. We studied the impact in survival according to the presence of the driver and the targeted therapy.

Results: Among the 261 patients included, oncodrivers alterations were found in 43.5% of patients: EML4-ALK fusion genes (2.1%), EGFR (10.3%), KRAS (27.7%), BRAF (2.5%), HER2 (0.8%), and PI3KCA (0.8%) mutations. Twenty-nine percent of patients (n=32) with oncodrivers received matched targeted therapy. Patient treated by targeted agent appropriate to an oncogenic driver had a median survival of 21.1 months (95% CI: 14.7-27.5). The patients (n=79) who did not receive targeted therapy had a median survival of 6.6 months (95% CI: 4.3-8.9). The patients (n=150) without identified driver had a median survival of 9.7 months (95% CI: 6.7-11.7); P<0.001.

Conclusion: An actionable oncodriver was routinely detected in nearly half of patients with advanced lung adenocarcinoma. This systematic detection may influence treatment outcomes, notably with matched targeted therapy.

Keywords: Biomarqueur; Cancer bronchique; Clinical trial; Essai clinique; Lung cancer; Oncogenic driver; Targeted therapy; Thérapie ciblée.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / mortality*
  • Adenocarcinoma / pathology
  • Adenocarcinoma of Lung
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / genetics*
  • Crizotinib
  • Early Detection of Cancer / methods
  • Female
  • Follow-Up Studies
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / pathology
  • Male
  • Mass Screening / methods
  • Middle Aged
  • Molecular Targeted Therapy*
  • Neoplasm Metastasis
  • Nuclear Proteins / genetics
  • Oncogene Proteins, Fusion / genetics
  • Oncogenes*
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Pyrazoles / therapeutic use
  • Pyridines / therapeutic use
  • Receptor, ErbB-2 / genetics
  • Survival Analysis
  • Transcription Factors / genetics

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • EML4-ALK fusion protein, human
  • KRAS protein, human
  • Nuclear Proteins
  • Oncogene Proteins, Fusion
  • PI3KCA protein, human
  • Pyrazoles
  • Pyridines
  • Transcription Factors
  • Crizotinib
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)