title: Gefitinib vs. chemotherapy as first-line therapy in advanced non-small cell lung cancer: meta-analysis of phase III trials.
abstract: BACKGROUND
  Gefitinib is an oral tyrosine kinase inhibitor against the epidermal growth factor receptor (EGFR). It has been shown to be active in patients with advanced non-small cell lung cancer (NSCLC) whose tumors contain EGFR mutations.
  
  
  METHODS
  We performed a meta-analysis of four randomized studies that compared gefitinib with chemotherapy in the first-line treatment of patients with advanced NSCLC: IPASS, North-East Japan, West Japan and first-SIGNAL studies. Patients were selected either on the basis of known EGFR mutations or based on clinicopathologic criteria - non-smokers with adenocarcinomas - associated with increased likelihood of EGFR mutations.
  
  
  RESULTS
  Nearly 2000 patients were enrolled on these four trials. Median ages ranged from 57 to 64years. Seventy-six percent were women and 86% were non-smokers. Overall, gefitinib was associated with significantly less toxicity than chemotherapy and improved quality-of-life. Gefitinib also produced higher response rates in the EGFR mutation-positive patients (72% vs. 38%, odds ratio 4.04, p<10(-15)), as well as improved progression-free survival (PFS; hazard ratio 0.45, p<10(-16)). Overall survival (OS) was not significantly different between treatment groups (p=0.35).
  
  
  CONCLUSIONS
  This meta-analysis confirms the results of each individual study and narrows the confidence intervals of these results. In patients with known EGFR mutations or whose tumors are likely to harbor a mutation, upfront gefitinib or chemotherapy are associated with similar OS. Gefitinib is associated with less fatigue, myelosuppression and nausea than chemotherapy (but produces more skin rash, diarrhea and pneumonitis). Patients receiving gefitinib have improved quality-of-life compared to those receiving chemotherapy, making it an appropriate first-line choice.
authors.affiliation: Johns Hopkins Singapore International Medical Center, Singapore. glopes@imc.jhmi.edu
authors.forename: Geoffrey Y
authors.initials: GY
authors.lastname: Ku
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Haaland
authors.forename: Gilberto
authors.initials: G
authors.lastname: de Lima Lopes
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D017326:Clinical Trials, Phase III as Topic; D004358:Drug Therapy; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D005260:Female; D000077156:Gefitinib; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009367:Neoplasm Staging; D011799:Quinazolines / Q000494:pharmacology / Q000627:therapeutic use*; D012907:Smoking; D016019:Survival Analysis
chemical_list: D011799:Quinazolines; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib