title: The role of bevacizumab in solid tumours: A literature based meta-analysis of randomised trials.
abstract: Bevacizumab is a humanised monoclonal antibody which blocks the binding of circulating vascular endothelial growth factor to its receptors. To date, the Food and Drug Administration has approved bevacizumab for the treatment of several solid tumours. To assess the impact of bevacizumab-based regimens on outcome in these advanced solid tumour types, we performed a meta-analysis. We included all of the randomised trials (phase II or III) where bevacizumab was tested in the first line setting compared with a control arm, including chemotherapy, placebo or other anti-neoplastic agents.
  
  
  
  A literature-based meta-analysis of randomised controlled trials (RCTs) in accordance with the preferences for reported items in systematic reviews and meta-analyses guidelines were undertaken. The primary end-point considered was overall survival (OS). The secondary end-points were progression-free survival (PFS) time, response rate and safety. A subgroup analysis was performed to highlight any differences between studies in different tumour types for all end-points.
  
  
  
  The pooled analysis from RCTs on bevacizumab-based regimens revealed significantly increased OS (hazard ratio [HR] for death 0.92, 95% confidence interval [CI]: 0.88-0.95; P < 0.0001), PFS (HR: 0.72, 95% CI: 0.67-0.78; P < 0.00001) and response rate (risk ratio: 1.38, 95% CI: 1.27-1.50; P < 0.00001) compared to control arm in solid tumours overall and in colorectal, lung, ovarian and renal cancer as single indications. However, notably, no effect on survival was seen in breast cancer.
  
  
  
  This study confirmed that bevacizumab-based regimens result in a significant effect on survival and response in advanced colorectal, lung, ovarian and kidney cancer. In cancers where bevacizumab failed overall as in breast cancer, a dedicated biomarkers analysis is warranted to select the proper subgroup of patient that might have the adequate clinical benefit.
authors.affiliation: Department of Oncology, Medical Oncology Unit, San Donato Hospital, Via Nenni 20, 52100 Arezzo, Italy; Department of Medical, Surgery and Health Sciences, University of Trieste, Piazza Ospitale 1, 34129 Trieste, Italy. Electronic address: giandomenicoroviello@gmail.com.
authors.forename: Giandomenico
authors.initials: G
authors.lastname: Roviello
authors.affiliation: Department of Medical Oncology, Centre Léon Bérard, Lyon, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bachelot
authors.affiliation: Memorial Sloan Kettering Cancer Center, 300 East 66th Street - 8th Floor, New York, NY 10065 USA; Weill Cornell Medical College, New York, NY USA.
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Hudis
authors.affiliation: European Institute of Oncology, Division of Experimental Therapeutics, Milano, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Curigliano
authors.affiliation: Tumour Biology Team, The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London SW3 6JB, England, UK.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Reynolds
authors.affiliation: Department of Oncology, Medical Oncology Unit, University of Siena, Viale Bracci 11, 53100 Siena, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Petrioli
authors.affiliation: Department of Medical, Surgery and Health Sciences, University of Trieste, Piazza Ospitale 1, 34129 Trieste, Italy; Unit of Molecular Therapy and Pharmacogenomic, ASST Cremona, Viale Concordia 1, 26100 Cremona, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Generali
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D018572:Disease-Free Survival; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000401:mortality; D009389:Neovascularization, Pathologic / Q000401:mortality / Q000517:prevention & control; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab
keywords: Angiogenesis; Bevacizumab; Solid tumours