title: Systematic review of the clinical effectiveness and cost-effectiveness, and economic evaluation, of denosumab for the treatment of bone metastases from solid tumours.
abstract: BACKGROUND
  Denosumab offers an alternative, or additional, treatment for the prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumours.
  
  
  OBJECTIVE
  The aim of this review was to assess the clinical effectiveness and cost-effectiveness of denosumab, within its licensed indication, for the prevention of SREs in patients with bone metastases from solid tumours.
  
  
  METHODS
  Databases searched were MEDLINE (1948 to April 2011), EMBASE (1980 to March 2011), The Cochrane Library (all sections; Issue 1, 2011) and Web of Science with Conference Proceedings (1970 to May 2011).
  
  
  METHODS
  Only randomised controlled trials (RCTs) assessing denosumab, bisphosphonates (BPs) or best supportive care (BSC) in patients with bone metastases were included. Systematic reviews and observational studies were used for safety and quality-of-life assessments. Study quality was assessed using the Cochrane risk of bias tool. Studies suitable for meta-analysis were synthesised using network meta-analysis (NMA). A systematic review was conducted for cost, quality-of-life and cost-effectiveness studies. The results of this informed the cost-utility modelling. This principally estimated the cost-effectiveness of denosumab relative to zoledronic acid for when BPs are currently recommended and relative to BSC when BPs are not recommended or are contraindicated.
  
  
  RESULTS
  A literature search identified 39 studies (eight suitable for NMA). Denosumab was effective in delaying time to first SRE and reducing the risk of multiple SREs compared with zoledronic acid. Generally speaking, denosumab was similar to zoledronic acid for quality of life, pain, overall survival and safety. The NMA demonstrated that denosumab was more effective in delaying SREs than placebo, but was limited by numerous uncertainties. Cost-utility modelling results for denosumab relative to zoledronic acid were driven by the availability of the patient access scheme (PAS) for denosumab. Without this, denosumab was not estimated to be cost-effective compared with zoledronic acid. With it, the cost-effectiveness ranged between dominance for breast and prostate cancer, to between £5400 and £15,300 per quality-adjusted life-year (QALY) for other solid tumours (OSTs) including non-small cell lung cancer (NSCLC) and £12,700 per QALY for NSCLC. Owing to small patient gains estimated, the cost-effectiveness of denosumab was very sensitive to the zoledronic acid price. Denosumab was not estimated to be cost-effective compared with BSC.
  
  
  CONCLUSIONS
  Only subgroup data were available for denosumab for NSCLC, and OSTs excluding NSCLC. The NMA was subject to numerous uncertainties. Owing to small patient gains estimated, the cost-effectiveness of denosumab was very sensitive to the zoledronic acid price.
  
  
  CONCLUSIONS
  Denosumab, compared with zoledronic acid and placebo, is effective in delaying SREs, but is similar with regard to quality of life and pain. Cost-effectiveness showed that without the PAS denosumab was not estimated to be cost-effective relative to either zoledronic acid or BSC. With the PAS, denosumab was estimated to be cost-effective relative to zoledronic acid but not BSC.
  
  
  BACKGROUND
  PROSPERO number CRD42011001418.
  
  
  BACKGROUND
  The National Institute for Health Research Health Technology Assessment programme.
authors.affiliation: Health Services Research Unit, University of Aberdeen, Aberdeen, UK.
authors.forename: J
authors.initials: J
authors.lastname: Ford
authors.forename: E
authors.initials: E
authors.lastname: Cummins
authors.forename: P
authors.initials: P
authors.lastname: Sharma
authors.forename: A
authors.initials: A
authors.lastname: Elders
authors.forename: F
authors.initials: F
authors.lastname: Stewart
authors.forename: R
authors.initials: R
authors.lastname: Johnston
authors.forename: P
authors.initials: P
authors.lastname: Royle
authors.forename: R
authors.initials: R
authors.lastname: Jones
authors.forename: C
authors.initials: C
authors.lastname: Mulatero
authors.forename: R
authors.initials: R
authors.lastname: Todd
authors.forename: G
authors.initials: G
authors.lastname: Mowatt
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000191:economics* / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000191:economics / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000378:metabolism*; D001943:Breast Neoplasms / Q000473:pathology; D003362:Cost-Benefit Analysis; D000069448:Denosumab; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology; D008297:Male; D018803:Models, Economic; D011471:Prostatic Neoplasms / Q000473:pathology; D019057:Quality-Adjusted Life Years; D016032:Randomized Controlled Trials as Topic
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents; D000069448:Denosumab