Abstract P6-07-02: Pharmacoeconomic evaluation of denosumab for the treatment of bone metastases in patients with advanced breast cancer in Canada
Authors: Habib MJ , Risebrough N , Moore P , Kendall R , Li CM , Goeree R 
Published: August 2014

Abstract
Background: Skeletal-related events (SREs) occur in 80% of patients with advanced breast cancer (BC) and bone metastases. SREs are costly and can be painful and debilitating, impacting patients’ quality of life and morbidity. While intravenous bisphosphonates such as pamidronate (PAM) and zoledronic acid (ZA) have demonstrated clinical benefit in reducing SREs, skeletal metastases remain a problem as treatments that are more efficacious, well tolerated, more convenient and less costly to administer are needed. Denosumab (XGEVA™) is a novel subcutaneous human monoclonal antibody therapy that significantly reduces the risk of developing SREs in patients with bone metastases from BC.
Objective: The objective of this project is to estimate the incremental cost-effectiveness of denosumab relative to ZA and PAM in the treatment of advanced BC patients with bone metastases.
Methods: A lifetime Markov model with four-week cycle lengths was developed with three health states: on treatment; off treatment; and death. The model included the risk of an SRE for patients on and off treatment and adverse events during treatment. Efficacy was measured as reduction in SREs. Head-to-head efficacy data, transition probabilities, and risk of adverse events were obtained from the clinical trial of denosumab versus ZA. (Stopeck AT et al JCO 2010) Efficacy data compared to PAM was determined from a published network meta-analysis. (Ford JA et al Eur J Cancer 2012) The baseline SRE risk was derived from clinical trial data due to the absence of real-world Canadian data. Analyses were conducted from the Canadian healthcare system perspective and reported in 2011 $CAD. Resource use was determined from a Canadian retrospective chart review of oncology patients with SREs. Costs were based on the published literature, the Ontario Case Costing Initiative, and input from a physician panel. Utility inputs were based on a time trade-off study. (Matza LS et al. Eur J Health Econ 2013) Bisphosphonate administration costs were derived from a published time and motion study. (Dranitsaris G et al. J Oncol Pharm Pract 2001) Outcomes were measured as both SREs avoided and quality-adjusted life years (QALYs) gained. Dominance was assessed or incremental cost-effectiveness ratios calculated per SRE avoided and per QALY gained, for denosumab compared to ZA and PAM. Future costs and QALYs were discounted at 5% per annum. Sensitivity analyses were conducted to test the robustness of the results.
Results: Denosumab was dominant and resulted in $5,733 in cost savings compared to ZA and $2,566 in cost savings compared to PAM based on a probabilistic analysis. Cost savings was driven by differences in drug administration costs and reduction in SREs. SREs avoided were 0.27 and 0.57 compared to ZA and PAM respectively. Denosumab resulted in 0.012 QALYs gained and 0.025 QALYs gained per patient compared to ZA and PAM, respectively. Sensitivity analyses showed the results were robust but most sensitive to drug administration costs and the relative risk of SREs.
Conclusion: Compared to both ZA and PAM, denosumab is more efficacious and offers better value for money (i.e. dominant) in Canada for managing SREs in patients with advanced BC and bone metastases.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-07-02.