title: The Efficacy of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors for Molecularly Selected Patients with Non-Small Cell Lung Cancer: A Meta-Analysis of 30 Randomized Controlled Trials.
abstract: OBJECTIVE
  To determine the efficacy of first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in molecularly selected patients with advanced non-small cell lung cancer (NSCLC), we performed this pooled analysis.
  
  
  METHODS
  Randomized trials of EGFR-TKIs as treatment for advanced NSCLC were included for this meta-analysis. We used published hazard ratios (HRs), if available, or derived treatment estimates from other survival data. Pooled estimates of treatment efficacy of EGFR-TKIs in the selected patients by EGFR-mutation status were calculated.
  
  
  RESULTS
  Out of 2134 retrieved articles, 30 randomized controlled trials (RCTs) enrolling more than 4053 patients with wild-type EGFR tumors and 1592 patients with mutant EGFR tumors were identified. For EGFR mutant patients, EGFR-TKIs treatment improved progression-free survival (PFS) compared with chemotherapy: the summary HRs were 0.41 (p < 0.00001) for the first-line setting and 0.46 (p = 0.02) for second/third-line setting, respectively. Also, the same superior trend was found with TKIs maintenance over placebo (HR = 0.14, p < 0.00001) and with TKIs combined with chemotherapy over chemotherapy (HR = 0.49, p = .002) in both the first-line and maintenance therapy settings. For EGFR wild-type patients, EGFR-TKIs have fared worse than chemotherapy in the first-line setting (HR = 1.65, p = .03) and in the second/third-line setting (HR = 1.27, p = .005). However, EGFR-TKIs maintenance still produced a reduction of 19 % in the risk of progression over placebo (HR = 0.81, p = .02). Furthermore, EGFR-TKIs added to chemotherapy as first-line treatment resulted in an improvement of PFS over chemotherapy alone in such wild-type EGFR patients (HR = 0.82, p = .03). In overall survival (OS) analysis, only EGFR-TKIs single agent was inferior to chemotherapy in EGFR wild-type patients (HR = 1.13, p = .02). No statistically significant difference in terms of OS was observed in any other subgroup analysis.
  
  
  CONCLUSIONS
  For EGFR mutant patients, EGFR-TKIs therapy produced a prominent PFS benefit in all settings. Among EGFR wild-type patients, EGFR-TKIs were inferior to chemotherapy both for first-line treatment and for second/third-line treatment. However, EGFR-TKIs maintenance and addition of EGFR-TKIs to chemotherapy could provide additive benefit over chemotherapy alone in such EGFR wild-type patients.
authors.affiliation: Shandong University, Jinan, Shandong, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Hematology, Weifang People's Hospital, Weifang, China.
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Sheng
authors.affiliation: Department of Oncology, Lin Yi People's Hospital, Linyi, 276003, China.
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Weifang Medical University, Weifang, Shandong, China. shengzhixin5569@163.com.
authors.forename: Guixin
authors.initials: G
authors.lastname: Li
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000401:mortality*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000401:mortality*; D058990:Molecular Targeted Therapy; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D015996:Survival Rate
chemical_list: D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors