title: Systematic review and meta-analysis of randomised, phase II/III trials adding bevacizumab to platinum-based chemotherapy as first-line treatment in patients with advanced non-small-cell lung cancer.
abstract: BACKGROUND
  Previous studies have demonstrated the efficacy and safety of bevacizumab in the treatment of non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Summary data from randomised trials comparing first-line bevacizumab plus platinum-based chemotherapy with chemotherapy alone for inoperable locally advanced, recurrent or metastatic NSCLC were meta-analysed. Pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and pooled odds ratio (OR) for adverse events were calculated. The chi-squared tests evaluated interactions between treatment effects, and prognostic factors and patient characteristics.
  
  
  RESULTS
  Data of 2194 patients (1313 bevacizumab; 881 controls) from four phase II and III trials: AVF-0757g, JO19907,ECOG 4599 and AVAiL, were analysed. Compared with chemotherapy alone, bevacizumab significantly prolonged OS(HR 0.90; 95% confidence interval [CI] 0.81, 0.99; P=0.03), and PFS (0.72; 95% CI 0.66, 0.79; P<0.001). Bevacizumab showed a significantly greater effect on OS in patients with adenocarcinoma versus other histologies (P=0.03), and patients with body weight loss ≤5% versus >5% (P=0.04). Bevacizumab significantly increased the risk of grade ≥3 proteinuria, hypertension,haemorrhagic events, neutropenia, and febrile neutropenia [corrected].
  
  
  CONCLUSIONS
  Bevacizumab significantly prolonged OS and PFS when added to first-line platinum-based chemotherapy in patients with advanced NSCLC; no unexpected toxicity was evident.
authors.affiliation: Department of Medicine, Institut Gustave Roussy, INSERM unit 981 and Paris University XI, Villejuif, France.
authors.forename: J-C
authors.initials: JC
authors.lastname: Soria
authors.forename: A
authors.initials: A
authors.lastname: Mauguen
authors.forename: M
authors.initials: M
authors.lastname: Reck
authors.forename: A B
authors.initials: AB
authors.lastname: Sandler
authors.forename: N
authors.initials: N
authors.lastname: Saijo
authors.forename: D H
authors.initials: DH
authors.lastname: Johnson
authors.forename: D
authors.initials: D
authors.lastname: Burcoveanu
authors.forename: M
authors.initials: M
authors.lastname: Fukuoka
authors.forename: B
authors.initials: B
authors.lastname: Besse
authors.forename: J-P
authors.initials: JP
authors.lastname: Pignon
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D000068258:Bevacizumab