title: Comparison of the efficacy and safety of EFGR tyrosine kinase inhibitor monotherapy with standard second-line chemotherapy in previously treated advanced non-small-cell lung cancer: a systematic review and meta-analysis.
abstract: OBJECTIVE
  To compare the efficacy and safety of epidermal growth factor receptor tyrosine kinase inhibitor monotherapy (EFGR-TKIs: gefitinib or erlotinib) with standard second-line chemotherapy (single agent docetaxel or pemetrexed) in previously treated advanced non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  We systematically searched for randomized clinical trials that compared EGFR-TKI monotherapy with standard second-line chemotherapy in previously treated advanced NSCLC. The end points were overall survival (OS), progression-free survival (PFS), overall response rate (ORR), 1-year survival rate (1-year SR) and grade 3 or 4 toxicities. The pooled hazard ratio (HR) or risk ratio (RR), with their corresponding 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials.
  
  
  RESULTS
  Eight randomized controlled trials (totally 3218 patients) were eligible. Our meta-analysis results showed that EGFR-TKIs were comparable to standard second-line chemotherapy for advanced NSCLC in terms of overall survival (HR 1.00, 95%CI 0.92-1.10; p=0.943), progression-free survival (HR 0.90, 95%CI 0.75-1.08, P=0.258) and 1-year-survival rate (RR 0.97, 95%CI 0.87-1.08, P=0.619), and the overall response rate was higher in patients who receiving EGFR-TKIs(RR 1.50, 95%CI 1.22-1.83, P=0.000). Sub-group analysis demonstrated that EGFR-TKI monotherapy significantly improved PFS (HR 0.73, 95%CI: 0.55-0.97, p=0.03) and ORR (RR 1.96, 95%CI: 1.46-2.63, p=0.000) in East Asian patients, but it did not translate into increase in OS and 1-year SR. Furthermore, there were fewer incidences of grade 3 or 4 neutropenia, febrile neutropenia and neurotoxicity in EGFR-TKI monotherapy group, excluding grade 3 or 4 rash.
  
  
  CONCLUSIONS
  Both interventions had comparable efficacy as second-line treatments for patients with advanced NSCLC, and EGFR-TKI monotherapy was associated with less toxicity and better tolerability. Moreover, our data also demonstrated that EGFR- TKI monotherapy tended to be more effective in East Asian patients in terms of PFS and ORR compared with standard second-line chemotherapy. These results should help inform decisions about patient management and design of future trials.
authors.affiliation: Department of Oncology, Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Wei-Xiang
authors.initials: WX
authors.lastname: Qi
authors.forename: Zan
authors.initials: Z
authors.lastname: Shen
authors.forename: Feng
authors.initials: F
authors.lastname: Lin
authors.forename: Yuan-Jue
authors.initials: YJ
authors.lastname: Sun
authors.forename: Da-Liu
authors.initials: DL
authors.lastname: Min
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Tang
authors.forename: Ai-Na
authors.initials: AN
authors.lastname: He
authors.forename: Yang
authors.initials: Y
authors.lastname: Yao
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D016022:Case-Control Studies; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D012196:Review Literature as Topic; D016879:Salvage Therapy
chemical_list: D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors