title: Gefitinib or erlotinib as maintenance therapy in patients with advanced stage non-small cell lung cancer: a systematic review.
abstract: BACKGROUND
  Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), gefitinib and erlotinib have been tested as maintenance therapy in patients with advanced non-small-cell lung cancer (NSCLC). The studies are quite heterogenous regarding study size and populations, and a synopsis of these data could give some more insight in the role of maintenance therapy with TKI.
  
  
  METHODS
  In September 2012 we performed a search in the pubmed, EMBASE and Cochrane library databases for randomized phase III trials exploring the role of gefitinib or erlotinib in advanced non-small cell lung cancer. Through a rigorous selection process with specific criteria, five trials (n = 2436 patients) were included for analysis. Standard statistical methods for meta-analysis were applied.
  
  
  RESULTS
  TKIs (gefitinib and erlotinib) significantly increased progression-free survival (PFS) [hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.50-0.76, I(2) = 78.1%] and overall survival (HR 0.84, 95% CI 0.76-0.93, I(2) = 0.0%) compared with placebo or observation. The PFS benefit was consistent in all subgroups including stage, sex, ethnicity, performance status, smoking status, histology, EGFR mutation status, and previous response to chemotherapy. Patients with clinical features such as female, never smoker, adenocarcinoma, Asian ethnicity and EGFR mutation positive had more pronounced PFS benefit. Overall survival benefit was observed in patients with clinical features such as female, non-smoker, smoker, adenocarcinoma, and previous stable to induction chemotherapy. Severe adverse events were not frequent. Main limitations of this analysis are that it is not based on individual patient data, and not all studies provided detailed subgroups analysis.
  
  
  CONCLUSIONS
  The results show that maintenance therapy with erlotinib or gefitinib produces a significant PFS and OS benefit for unselected patients with advanced NSCLC compared with placebo or observation. Given the less toxicity of TKIs than chemotherapy and simple oral administration, this treatment strategy seems to be of important clinical value.
authors.affiliation: Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Chen
authors.forename: Yiqian
authors.initials: Y
authors.lastname: Liu
authors.forename: Oluf Dimitri
authors.initials: OD
authors.lastname: Røe
authors.forename: Yingying
authors.initials: Y
authors.lastname: Qian
authors.forename: Renhua
authors.initials: R
authors.lastname: Guo
authors.forename: Lingjun
authors.initials: L
authors.lastname: Zhu
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Yin
authors.forename: Yongqian
authors.initials: Y
authors.lastname: Shu
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib
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