title: Efficacy of EGFR tyrosine kinase inhibitors in non-small-cell lung cancer patients with/without EGFR-mutation: evidence based on recent phase III randomized trials.
abstract: BACKGROUND
  EGFR mutation might be a predictive factor for applying EGFR-tyrosine kinase inhibitors (EGFR-TKIs, including gefitinib, erlotinib and afatinib) in non-small-cell lung cancer (NSCLS) patients. Thus, it is necessary to pool previous trials to compare the effect of EGFR-TKIs versus cytotoxic chemotherapy in EGFR mutation positive (mut+) and negative (mut-) patients.
  
  
  METHODS
  This study identified 8 first-line and 9 second-line phase III trials in databases. Hazard ratio (HR) was pooled to assess the risk of progression-free survival (PFS), and overall survival (OS), while odds ratio (OR) was pooled to assess objective response, disease control, and toxicity of EGFR-TKIs verses chemotherapy.
  
  
  RESULTS
  In EGFR mut+ patients, EGFR-TKIs were associated with significantly lower risk of disease progression in the first-line setting, but this trend was only observed in the gefitinib group, not in the erlotinib group in the second-line setting. In EGFR mut- patients, gefitinib and erlotinib had significantly higher risk of disease progression in first-line and second-line setting, respectively. Compared with chemotherapy, the effects of EGFR-TKIs on OS in both first-line and second-line settings were not evident. Regarding toxicity, EGFR-TKIs had significantly higher risk of rash and lower hematological toxicity compared with chemotherapy.
  
  
  CONCLUSIONS
  All of the 3 EGFR-TKIs and gefitinib alone regimens had better effects in prolonging PFS in EGFR mut+ patients in first-line and second-line setting, respectively, but chemotherapy seemed more effective in EGFR mut- patients than EGFR-TKIs. Therefore, accurate identification of EGFR mutation status is useful to decide on an appropriate regimen for treatment of NSCLC patients.
authors.affiliation: Department of Thoracic Surgery, Beijing Institute of Respiratory Diseases, Beijing Chaoyang Hospital, Capital Medical University, Bejing, China (mainland).
authors.forename: Wen-Qian
authors.initials: WQ
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Beijing Institute of Respiratory Diseases, Beijing Chaoyang Hospital, Capital Medical University, Bejing, China (mainland).
authors.forename: Tong
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, Beijing Institute of Respiratory Diseases, Beijing Chaoyang Hospital, Capital Medical University, Bejing, China (mainland).
authors.forename: Hui
authors.initials: H
authors.lastname: Li
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D017326:Clinical Trials, Phase III as Topic; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors