BACKGROUND: Bone metastases are common in patients with hormone-refractory 
prostate cancer. In a study of autopsies of patients with prostate cancer, 
65%-75% had bone metastases. Bone metastases place a substantial economic burden 
on payers with estimated total annual costs of $1.9 billion in the United 
States. Skeletal-related events (SREs), including pathologic fractures, spinal 
cord compression, surgery to bone, and radiation to bone, affect approximately 
50% of patients with bone metastases. They are associated with a decreased 
quality of life and increased health care costs. Zoledronic acid is an effective 
treatment in preventing SREs in solid tumors and multiple myeloma. Recently, 
denosumab was FDA-approved for prevention of SREs in patients with bone 
metastases from solid tumors. A Phase 3 clinical trial (NCT00321620) 
demonstrated that denosumab had superior efficacy in delaying first and 
subsequent SREs compared with zoledronic acid. However, the economic value of 
denosumab has not been assessed in patients with hormone-refractory prostate 
cancer.
OBJECTIVE: To compare the cost-effectiveness of denosumab with zoledronic acid 
in the treatment of bone metastases in men with hormone-refractory prostate 
cancer.
METHODS: An Excel-based Markov model was developed to assess costs and 
effectiveness associated with the 2 treatments over a 1- and 3-year time 
horizon. Because the evaluation was conducted from the perspective of a U.S. 
third-party payer, only direct costs were included. Consistent with the primary 
outcome in the Phase 3 trial, effectiveness was assessed based on the number of 
SREs. The model consisted of 9 health states defined by SRE occurrence, SRE 
history, disease progression, and death. A hypothetical cohort of patients with 
hormone-refractory prostate cancer received either denosumab 120 mg or 
zoledronic acid 4 mg at the model entry and transitioned among the 9 health 
states at the beginning of each 13-week cycle. Transition probabilities 
associated with experiencing the first SRE, subsequent SREs, disease 
progression, and death were primarily derived from the results of the Phase 3 
clinical trial and were supplemented with published literature. The model 
assumed that a maximum of 1 SRE could occur in each cycle. Drug costs included 
wholesale acquisition cost, health care professional costs associated with drug 
administration, and drug monitoring costs, if applicable. Nondrug costs included 
incremental costs associated with disease progression, costs associated with 
SREs, and terminal care costs, which were derived from the literature. Adverse 
event (AE) costs were estimated based on the incidence rates reported in the 
Phase 3 trial. Resource utilization associated with AEs was estimated based on 
consultation with a senior medical director employed by the study sponsor. All 
costs were presented in 2010 dollars. The base case estimated the incremental 
total cost per SRE avoided over a 1-year time horizon. Results for a 3-year time 
horizon were also estimated. One-way sensitivity analyses and probabilistic 
sensitivity analyses (PSA) were performed to test the robustness of the model.
RESULTS: In the base case, the total per patient costs incurred over 1 year were 
estimated at $35,341 ($19,230 drug costs and $16,111 nondrug costs) for 
denosumab and $27,528 ($10,960 drug costs and $16,569 nondrug costs) for 
zoledronic acid, with an incremental total direct cost of $7,813 for denosumab. 
The estimated numbers of SREs per patient during the 1-year period were 0.49 for 
denosumab and 0.60 for zoledronic acid, resulting in an incremental number of 
SREs of -0.11 in the denosumab arm. The estimated incremental total direct costs 
per SRE avoided with the use of denosumab instead of zoledronic acid were 
$71,027 for 1 year and $51,319 for 3 years. The 1-way sensitivity analysis 
indicated that the results were sensitive to the drug costs, median time to 
first SRE, and increased risk of SRE associated with disease progression. 
Results of the PSA showed that based on willingness-to-pay thresholds of 
$70,000, $50,000, and $30,000 per SRE avoided, respectively, denosumab was 
cost-effective compared with zoledronic acid in 49.5%, 17.5%, and 0.3% of the 
cases at 1 year, respectively, and 79.0%, 49.8%, and 4.1% of the cases at 3 
years, respectively.
CONCLUSIONS: Although denosumab has demonstrated benefits over zoledronic acid 
in preventing or delaying SREs in a Phase 3 trial, it may be a costly 
alternative to zoledronic acid from a U.S. payer perspective.