title: Bevacizumab in the treatment of advanced, non-squamous non-small cell lung cancer: an evidence-based approach.
abstract: BACKGROUND
  To assess the efficacy and safety of bevacizumab-containing regimens in the treatment of advanced, chemotherapy-naive, non-squamous non-small cell lung cancer (NSCLC) on the basis of the two registrative trials [ECOG E4599 trial and BO17704 (AVAiL) trial].
  
  
  METHODS
  A pooled analysis of the two trials was performed using a random effect model, and the results were summarized as number-needed-to-treat (NNT) and number-needed-to-harm (NNH). A 2-step analysis was performed. The primary analysis included only the patients treated with bevacizumab 15 mg/kg in the experimental arm, whereas the secondary analysis (with descriptive aim) included the patients treated with bevacizumab 15 mg/kg or those treated with bevacizumab 7.5 mg/kg in the experimental arm. The 1-year survival and 6-month progression-free rates were assumed as indexes of efficacy, and grade III-IV side effects were assumed as index of safety in both analyses.
  
  
  RESULTS
  1,921 patients were potentially eligible for the pooled analysis and were included in the secondary analysis, whereas 1,576 patients were included in the primary analysis. A large heterogeneity was documented for both 6-month progression-free interval (I(2) = 88.164%, p = 0.004) and overall survival (I(2) = 73.541, p = 0.052). The absolute risk reduction of 1-year death and 6-month progression were 3.3% (95% CI = -6.5 to 13.2%, p = 0.507), with a NNT = 30; and 15.2% (95% CI = 0.07-29.6%, p = 0.04), with a NNT = 6 (both in favor of the bevacizumab-containing regimens), respectively. The absolute risk of treatment-related death was 2.4% (95% CI = 0.8-3.9%, p = 0.003), with a NNH = 41 against the bevacizumab-containing regimens; that of bleeding was 3.3% (95% CI = 1.6-4.9%, p < 0.001), with a NNH = 30; that of hypertension was 6.6% (95% CI = 4.6-8.6%, p < 0.001), with a NNH = 15; that of proteinuria was 2.1% (95% CI = 0.3-3.8%, p = 0.024), with a NNH = 47; that of neutropenia was 7.3% (95% CI = 3.2-11.4%, p < 0.001), with a NNH = 13; that of thrombocytopenia was 1.5% (95% CI = 0.2-2.7%, p = 0.021), with a NNH = 66. No significant differences were observed in the efficacy and the safety analysis when all the patients treated with bevacizumab 7.5 mg/kg and 15 mg/kg were included into the pooled analysis.
  
  
  CONCLUSIONS
  Adding bevacizumab to standard chemotherapy in the treatment of advanced, chemotherapy-naive, non-squamous NSCLC seems to favor a modest improvement in the main outcomes, with a significant worsening of the safety profile. These data suggest caution in the generalized use of bevacizumab-containing regimens in the treatment of advanced, chemotherapy-naive, non-squamous NSCLC.
authors.affiliation: Department of Oncology, City Hospital, Rimini, Italy. dtassinari@rimini.com
authors.forename: Davide
authors.initials: D
authors.lastname: Tassinari
authors.forename: Sergio
authors.initials: S
authors.lastname: Sartori
authors.forename: Maximilian
authors.initials: M
authors.lastname: Papi
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Drudi
authors.forename: Cinzia
authors.initials: C
authors.lastname: Castellani
authors.forename: Federica
authors.initials: F
authors.lastname: Carloni
authors.forename: Paola
authors.initials: P
authors.lastname: Tombesi
authors.forename: Luigi
authors.initials: L
authors.lastname: Lazzari-Agli
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D019317:Evidence-Based Medicine; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D008175:Lung Neoplasms / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced; D011507:Proteinuria / Q000139:chemically induced; D016032:Randomized Controlled Trials as Topic; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab