Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: A cost-effectiveness analysis

Abstract

Objective:

Denosumab has been approved in the US for skeletal-related event (SRE) prevention in bone-metastatic prostate cancer on the basis of a phase III clinical trial in which denosumab reduced SREs relative to zoledronic acid. Overall survival, disease progression, and serious adverse events did not differ significantly between groups. This analysis assessed the cost-effectiveness of denosumab vs zoledronic acid in bone-metastatic prostate cancer from a US payer perspective.

Methods:

A literature-based Markov model, wherein inputs were selected to reproduce clinical trial outcomes, was developed to estimate the survival, quality-adjusted life-years (QALYs), number and costs of SREs, and drug and administration costs for patients receiving denosumab or zoledronic acid over 27 months. QALYs were estimated by assigning health-state utilities. SRE-related costs and utilities were literature-based. Outcomes were discounted 3% per annum, and model robustness was tested via scenario, univariate, and probabilistic sensitivity analyses.

Results:

Denosumab resulted in fewer estimated SREs (−0.241; 1.036 vs 1.277), more QALYs (0.0074; 0.9306 vs 0.9232), and lower SRE-related costs (−$2340; $8824 vs $11,164), but higher drug-related costs ($10,181; $23,144 vs $12,963) and total costs ($7841; $31,968 vs $24,127) vs zoledronic acid. The base case estimated cost per QALY-gained was $1,058,741.

Conclusion:

This analysis was limited by the restricted availability of clinical data and the need to use projection methods beyond the trial time frame. However, a wide range of scenarios predicted denosumab to have an incremental cost/QALY gained above what may be considered acceptable value for money in the US. This raises important questions regarding the pharmacoeconomic value of denosumab in bone-metastatic prostate cancer.

Key words::

• Denosumab
• Zoledronic acid
• Cost-effectiveness
• Prostate cancer
• Bone metastases
• Skeletal-related event

Transparency

Declaration of funding

SJS, JAC, and MFB received a consulting fee from Novartis Pharmaceuticals (maker of zoledronic acid) related to the development of this analysis.

Declaration of financial/other relationships

SK was an employee of and stock owner in Novartis Pharmaceuticals at the time that the analysis was first drafted. SK is now an employee of Celgene Corporation and no longer owns stock in Novartis Pharmaceuticals. The peer reviewers on this manuscript have disclosed that they have no other relevant financial relationships.

Acknowledgements

No additional funding or outside assistance was obtained for this analysis and/or manuscript. An earlier version of this analysis was presented as a poster (#4581) at the 2011 ASCO Annual Meeting; June 3–7, 2011; Chicago, IL.