title: Cost-effectiveness of denosumab versus zoledronic acid in the management of skeletal metastases secondary to breast cancer.
abstract: BACKGROUND
  Denosumab has been approved in the United States for the prevention of skeletal-related events (SREs) in metastatic breast cancer. In a Phase III trial in patients with bone-metastatic breast cancer (N = 2033), denosumab was associated with a significantly delayed time to first SRE (by 18%; P < 0.001 noninferiority; P = 0.01 superiority) and time to first and subsequent SREs (by 23%; P = 0.001). Overall survival (HR = 0.95; 95% CI, 0.81-1.11; P = 0.49) and disease progression (HR = 1.00; 95% CI, 0.89-1.11; P = 0.93) did not differ significantly between groups. Denosumab was associated with a nonsignificant reduction in serious adverse events (44.4% vs 46.5%).
  
  
  OBJECTIVE
  Given the current ambiguity regarding the cost-effectiveness of these agents in light of these trial outcomes, the present analysis assessed, from a US payer perspective, the cost-effectiveness of denosumab versus zoledronic acid in patients with bone metastases secondary to breast cancer.
  
  
  METHODS
  A literature-based Markov model was developed to estimate the survival, quality-adjusted life-years (QALYs) gained, number and costs of SREs, and drug and administration costs in patients receiving denosumab or zoledronic acid over 27 and 60 months. Clinical inputs reproduced the trial outcomes. SRE-related costs and utilities were literature based. Costs and QALYs were discounted 3% annually.
  
  
  RESULTS
  In the 27-month base-case analysis, denosumab was associated with fewer SREs (-0.298), more QALYs (+0.0102), and lower SRE-related costs (-$2016), but higher drug-related (+$9123) and total costs (+$7107) versus zoledronic acid. The cost per QALY gained (ie, incremental cost-effectiveness ratio [ICER]) was $697,499. In sensitivity analyses, the ICER ranged from $192,472 to $1,340,901/QALY, depending on assumptions regarding treatment benefits, drug costs, and analytical horizon. In the probabilistic sensitivity analysis, denosumab was cost-effective in 2 of 5000 modeled replicates (0.04%).
  
  
  CONCLUSIONS
  Despite the limitations of restricted availability of clinical data and uncertainty regarding the price of generic zoledronic acid, the findings from the present analysis suggest that the use of denosumab is associated with a high ICER compared with zoledronic acid. This finding may raise important questions regarding the economic value of denosumab in bone-metastatic breast cancer.
authors.affiliation: Pharmerit North America LLC, Bethesda, MD 20814, USA.
authors.forename: Sonya J
authors.initials: SJ
authors.lastname: Snedecor
authors.forename: John A
authors.initials: JA
authors.lastname: Carter
authors.forename: Satyin
authors.initials: S
authors.lastname: Kaura
authors.forename: Marc F
authors.initials: MF
authors.lastname: Botteman
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary; D001943:Breast Neoplasms / Q000473:pathology*; D003362:Cost-Benefit Analysis; D000069448:Denosumab; D004164:Diphosphonates / Q000627:therapeutic use*; D016527:Drug Costs; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D011788:Quality of Life; D019057:Quality-Adjusted Life Years; D000077211:Zoledronic Acid
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D004164:Diphosphonates; D007093:Imidazoles; D000069448:Denosumab; D000077211:Zoledronic Acid