title: Cost-effectiveness of denosumab vs zoledronic acid for prevention of skeletal-related events in patients with solid tumors and bone metastases in the United States.
abstract: OBJECTIVE
  With increasing healthcare resource constraints, it has become important to understand the incremental cost-effectiveness of new medicines. Subcutaneous denosumab is superior to intravenous zoledronic acid (ZA) for the prevention of skeletal-related events (SREs) in patients with advanced solid tumors and bone metastases. This study sought to determine the lifetime cost-effectiveness of denosumab vs ZA in this setting, from a US managed-care perspective.
  
  
  METHODS
  A lifetime Markov model was developed, with relative rate reductions in SREs for denosumab vs ZA derived from three pivotal Phase 3 trials involving patients with castration-resistant prostate cancer (CRPC), breast cancer, and non-small-cell lung cancer (NSCLC), and bone metastases. The real-world SRE rates in ZA-treated patients were derived from a large commercial database. SRE and treatment administration quality-adjusted life year (QALY) decrements were estimated with time-trade-off studies. SRE costs were estimated from a nationally representative commercial claims database. Drug, drug administration, and renal monitoring costs were included. Costs and QALYs were discounted at 3% annually. One-way and probabilistic sensitivity analyses were conducted.
  
  
  RESULTS
  Across tumor types, denosumab was associated with a reduced number of SREs, increased QALYs, and increased lifetime total costs vs ZA. The costs per QALY gained for denosumab vs ZA in CRPC, breast cancer, and NSCLC were $49,405, $78,915, and $67,931, respectively, commonly considered good value in the US. Costs per SRE avoided were $8567, $13,557, and $10,513, respectively. Results were sensitive to drug costs and SRE rates.
  
  
  CONCLUSIONS
  Differences in pain severity and analgesic use favoring denosumab over ZA were not captured. Mortality was extrapolated from fitted generalized gamma function beyond the trial duration.
  
  
  CONCLUSIONS
  Denosumab is a cost-effective treatment option for the prevention of SREs in patients with advanced solid tumors and bone metastases compared to ZA. The overall value of denosumab is based on superior efficacy, favorable safety, and more efficient administration.
authors.affiliation: University of Arizona Cancer Center, Tucson, AZ 85724-5024, USA. astopeck@azcc.arizona.edu
authors.forename: Alison
authors.initials: A
authors.lastname: Stopeck
authors.forename: Michael
authors.initials: M
authors.lastname: Rader
authors.forename: David
authors.initials: D
authors.lastname: Henry
authors.forename: Mark
authors.initials: M
authors.lastname: Danese
authors.forename: Marc
authors.initials: M
authors.lastname: Halperin
authors.forename: Ze
authors.initials: Z
authors.lastname: Cong
authors.forename: Yi
authors.initials: Y
authors.lastname: Qian
authors.forename: Roger
authors.initials: R
authors.lastname: Dansey
authors.forename: Karen
authors.initials: K
authors.lastname: Chung
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000191:economics* / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000191:economics* / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D017326:Clinical Trials, Phase III as Topic; D003362:Cost-Benefit Analysis; D000069448:Denosumab; D004164:Diphosphonates / Q000191:economics* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000191:economics* / Q000627:therapeutic use; D008297:Male; D008390:Markov Chains; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019057:Quality-Adjusted Life Years; D014481:United States; D000077211:Zoledronic Acid
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000069448:Denosumab; D000077211:Zoledronic Acid