title: Use of the epidermal growth factor receptor inhibitors gefitinib, erlotinib, afatinib, dacomitinib, and icotinib in the treatment of non-small-cell lung cancer: a systematic review.
abstract: BACKGROUND
  This systematic review addresses the use of epidermal growth factor receptor (egfr) inhibitors in three populations of advanced non-small-cell lung cancer (nsclc) patients-unselected, selected, and molecularly selected-in three treatment settings: first line, second line, and maintenance.
  
  
  METHODS
  Ninety-six randomized controlled trials found using the medline and embase databases form the basis of this review.
  
  
  RESULTS
  In the first-line setting, data about the efficacy of egfr tyrosine kinase inhibitors (tkis) compared with platinum-based chemotherapy are inconsistent. Results from studies that selected patients based on clinical characteristics are also mixed. There is high-quality evidence that an egfrtki is preferred over a platinum doublet as initial therapy for patients with an activating mutation of the EGFR gene. The egfrtkis are associated with a higher likelihood of response, longer progression-free survival, and improved quality of life. Multiple trials of second-line therapy have compared an egfrtki with chemotherapy. Meta-analysis of those data demonstrates similar progression-free and overall survival. There is consequently no preferred sequence for second-line egfrtki or second-line chemotherapy. The egfrtkis have also been evaluated as switch-maintenance therapy. No molecular marker could identify patients in whom a survival benefit was not observed; however, the magnitude of the benefit was modest.
  
  
  CONCLUSIONS
  Determination of EGFR mutation status is essential to making appropriate treatment decisions in patients with nsclc. Patients who are EGFR mutation-positive should be treated with an egfrtki as first-line therapy. An egfrtki is still appropriate therapy in patients who are EGFR wild-type, but the selected agent should be administered as second- or third-line therapy.
authors.affiliation: Department of Oncology, McMaster University, Hamilton, ON; ; Juravinski Cancer Centre, Hamilton, ON;
authors.forename: P M
authors.initials: PM
authors.lastname: Ellis
authors.affiliation: Department of Oncology, McMaster University, Hamilton, ON; ; Cancer Care Ontario, Program in Evidence-Based Care, Hamilton, ON;
authors.forename: N
authors.initials: N
authors.lastname: Coakley
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, and University Health Network, University of Toronto, Toronto, ON;
authors.forename: R
authors.initials: R
authors.lastname: Feld
authors.affiliation: Department of Oncology, The University of Western Ontario, and London Regional Cancer Program, London, ON;
authors.forename: S
authors.initials: S
authors.lastname: Kuruvilla
authors.affiliation: Department of Radiation Oncology, University of Toronto, and Odette Cancer Centre, Toronto, ON.
authors.forename: Y C
authors.initials: YC
authors.lastname: Ung
keywords: Non-small-small cell lung cancer; egfr inhibitors; mutation status; systematic review