Prospective Evaluation of First-Line Erlotinib in Advanced Non-Small Cell Lung Cancer (NSCLC) Carrying an Activating EGFR Mutation: A Multicenter Academic Phase II Study in Caucasian Patients (FIELT)

PLoS One. 2016 Mar 31;11(3):e0147599. doi: 10.1371/journal.pone.0147599. eCollection 2016.

Abstract

Introduction: Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibition is the preferred first-line treatment of advanced adenocarcinoma of the lung that harbors EGFR activating tyrosine kinase domain mutations. Most data available pertain to Asian populations in which such mutations are more prevalent. We report on the long-term results of first-line treatment with erlotinib in Caucasian patients with advanced adenocarcinoma of the lung that have a somatic EGFR mutation in their tumor.

Methods: Multicenter academic prospective phase II study with erlotinib in patients with an activating EGFR tyrosine kinase (TK) domain somatic mutation (any exon encoding the kinase domain) in the tumor and no prior treatment for their advanced disease.

Results: Phenotypic preselecting of 229 patients led to a high EGFR mutation detection rate of 24% of which 46 patients were included in the phase II study. With a progression free survival (PFS) of 81% at three months the study met its primary endpoint for presumed superiority over chemotherapy. With an overall median PFS of 11 months and a median overall survival (OS) of 23 months, the results compare favorably with results obtained in randomized studies using TKI in first line in EGFR mutation positive adenocarcinoma of the lung.

Conclusion: The present study reinforces the use of EGFR tyrosine kinase inhibition (TKI) as a first line treatment of choice for advanced adenocarcinoma of the lung carrying an activating EGFR mutation. The mutation rate in preselected Caucasian patients is higher than previously reported. Issues relevant for clinical practice are discussed.

Trial registration: ClinicalTrials.gov NCT00339586.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • DNA Mutational Analysis
  • ErbB Receptors / genetics*
  • Erlotinib Hydrochloride / adverse effects
  • Erlotinib Hydrochloride / therapeutic use*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Prospective Studies
  • Survival Analysis
  • Treatment Outcome
  • White People / genetics*

Substances

  • Erlotinib Hydrochloride
  • ErbB Receptors

Associated data

  • ClinicalTrials.gov/NCT00339586

Grants and funding

This work was supported by the following sources of funding: Stichting Tegen Kanker STK (JDG); Wetenschappelijk Fonds Willy Gepts UZ Brussel (JDG); Cancer plan 19 Grant 29-039 (JDG); and Roche Belgium (JDG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.