title: The Efficacy of Single-Agent Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy in Biologically Selected Patients with Non-Small-Cell Lung Cancer: A Meta-Analysis of 19 Randomized Controlled Trials.
abstract: OBJECTIVE
  To determine the efficacy of first-generation single-agent epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy in advanced non-small-cell lung cancer patients with known EGFR mutation status, we undertook this pooled analysis.
  
  
  METHODS
  We searched for randomized controlled trials (RCTs) in Medline, Embase, the Cochrane Controlled Trials Register, the Science Citation Index, and the American Society of Clinical Oncology annual meetings.
  
  
  RESULTS
  Out of 2,129 retrieved articles, 19 RCTs enrolling 2,016 patients with wild-type EGFR tumors and 1,034 patients with mutant EGFR tumors were identified. For these EGFR mutant patients, single-agent EGFR-TKI therapy improved progression-free survival (PFS) over chemotherapy: the summary hazard ratios (HRs) were 0.41 (p < 0.001) for the first-line setting and 0.46 (p = 0.02) for the second-/third-line setting. For those EGFR wild-type patients, single-agent EGFR-TKI therapy did not do as well as chemotherapy in the first-line setting (HR = 1.65, p = 0.03) and in the second-/third-line setting (HR = 1.27, p = 0.006). No statistically significant difference was observed in terms of overall survival (OS). Using platinum-based doublet chemotherapy as a common comparator, indirect comparison showed the superior efficacy of single-agent EGFR-TKI therapy over EGFR-TKIs added to chemotherapy in PFS [HR = 1.35 (1.03, 1.77), p = 0.03]. Additionally, a marginal trend towards the same direction was found in the OS analysis [HR = 1.16 (0.99, 1.35), p = 0.06]. Interestingly, for those EGFR wild-type tumors, single-agent EGFR-TKI therapy was inferior to EGFR-TKIs added to chemotherapy in PFS [HR = 0.38 (0.33, 0.44), p < 0.001] and OS [HR = 0.83 (0.71, 0.97), p = 0.02].
  
  
  CONCLUSIONS
  For these EGFR mutant patients, single-agent EGFR-TKI therapy prolonged PFS over chemotherapy. However, single-agent EGFR-TKI therapy was inferior to chemotherapy in PFS for those EGFR wild-type patients. Single-agent EGFR-TKI therapy could improve PFS over the combination of EGFR-TKIs and chemotherapy in these EGFR mutant patients. However, EGFR-TKIs combined with chemotherapy could provide additive PFS and OS benefit over single-agent EGFR-TKI therapy in those EGFR wild-type patients.
authors: Guifang
authors: G
authors: Li
authors: Shunji
authors: S
authors: Gao
authors: Zhixin
authors: Z
authors: Sheng
authors: Bin
authors: B
authors: Li
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D016208:Databases, Factual; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D015996:Survival Rate
chemical_list: D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors