Beyond the Abstract - Economic evaluation of denosumab compared with zoledronic acid in hormone-refractory prostate cancer patients with bone metastases, by Jipan Xie, MD, PhD

BERKELEY, CA (UroToday.com) -

Commentary on the Cost-Effectiveness of Denosumab vs. Zoledronic Acid in Hormone-Refractory Prostate Cancer Patients with Bone Metastases


Denosumab was approved by the Food and Drug Administration (FDA) in 2010 for the prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumors. In a large phase III clinical trial, denosumab was shown to be more efficacious than zoledronic acid (ZA) in preventing and delaying first and subsequent on-study SREs in hormone-refractory prostate cancer (HRPC) patients with bone metastases.1 However, given the substantial difference in drug costs between the two treatments ($878 for ZA vs. $1,650 for denosumab per 4 weeks, November 2010), it would be natural to ask whether it is cost-effective to use denosumab instead of ZA in this population. To address this question, we conducted a cost-effectiveness analysis (CEA) from a third-party payer perspective in the U.S.2

With limited health care resources, decision makers become increasingly attentive to the economic values of different treatments. Using a large randomized controlled trial, our study provides valuable information to payers about the cost-effectiveness of denosumab vs. zoledronic acid in the treatment of HRPC patients with bone metastases.

The CEA was based on a Markov model comprised of 9 health states defined by SRE occurrence, SRE history, progression, and death, which accounted for all important clinical outcomes in HRPC patients with bone metastases. The outcome of the CEA was the incremental direct costs per SRE avoided. We chose SRE instead of quality-adjusted life year (QALY) mainly for two reasons. First, SRE was the primary outcome in the phase III trial. Second, there was little difference in progression rate and survival between denosumab and ZA in the phase III trial; thus, using QALY as an outcome may not be able to differentiate the two treatments.

Model inputs were drawn from the literature and public data sources. Transitional probabilities between the 9 health states were largely derived from the published phase III trial.1 The model considered a comprehensive list of direct costs from a U.S. payer perspective, including drug, drug administration and monitoring costs, costs of SREs, costs associated with disease progression, and costs of adverse events.

Several key assumptions in the model estimation are worth mentioning. First, the model assumed that no more than 1 SRE could occur in each cycle (i.e., 13 weeks), which is consistent with the mean time separating 2 types of SREs in the literature.3 Second, transitional probabilities were assumed to be constant. Third, the model assumed that progression in HRPC increased the risk of SRE by 2.14 fold, as estimated in previous research.4

Results from the CEA showed that denosumab-treated patients had $8,270 more drug and drug administration costs than ZA-treated patients in the first year. Although denosumab-treated patients could potentially save $458 in other costs (primarily from reduced SRE costs), this amount was not enough to offset the substantially higher drug costs in this treatment group. Thus, the total direct costs difference ($7,813) was largely driven by the variation in drug costs. In terms of effectiveness, denosumab was associated with 0.11 fewer SREs by the end of the first year. In combination, the total direct cost per SRE avoided associated with the use of denosumab vs. ZA was estimated to be $71,027 by the end of the first year. The study also estimated that the total direct cost per SRE avoided to be $51,319 by the end of three years. However, the 3-year results may not be applicable to the real world because the generic form of ZA is expected to be available in March 2013, which may further increase the difference in the drug costs between denosumab and ZA.

Although there is no clear threshold of a payer’s willingness-to-pay (WTP) to avoid one SRE, the incremental costs per SRE avoided in the study seems to be high compared to the results from similar studies, which were below $20,000 per SRE avoided.5, 6 To further understand the cost-effectiveness of denosumab vs. ZA, we performed an analysis using QALY as the outcome. The disutility of SREs was applied to the cycle when an SRE occurred. The results showed that total direct cost per QALY gained comparing denosumab vs. ZA was $3.91 million, far exceeding the WTP threshold for cancer patients. This additional analysis, combined with the main findings, suggest that denosumab may not be a cost-effective alternative among HRPC patients with bone metastases.

As with any economic modeling, the results in this CEA are subject to the goodness of the model assumptions. To test the robustness of the results, we conducted extensive sensitivity analyses by varying model assumptions from the base case. The majority of one-way sensitivity analyses estimated the total direct costs per SRE avoided to be over $50,000. The total direct costs per SRE were less than $50,000 when denosumab drug cost decreased by 25%, ZA drug cost increased by 25%, median time to first on-study SRE increased to the 95% upper limit for denosumab, or median time to first on-study SRE decreased to the 95% lower limit for ZA. Under probabilistic sensitivity analyses, denosumab had a 17.5% chance of being cost-effective if the payer’s willingness-to-pay threshold for an SRE avoided was $50,000. These sensitivity analyses suggest that the results are robust.

With limited health care resources, decision makers become increasingly attentive to the economic values of different treatments. Using a large randomized controlled trial, our study provides valuable information to payers about the cost-effectiveness of denosumab vs. ZA in the treatment of HRPC patients with bone metastases. Future economic evaluations may be conducted in a real-world setting when additional data become available.

References:

  1. Fizazi K, Carducci M, Smith M, et al. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet. 2011;377(9768):813-22.
  2. Xie J, Namjoshi M, Wu EQ, Parikh K, Diener M, Yu AP, et al. Economic evaluation of denosumab compared with zoledronic acid in hormone-refractory prostate cancer patients with bone metastases. J Manag Care Pharm. 2011;17(8):621-34.
  3. Lage MJ, Barber BL, Harrison DJ, Jun S. The cost of treating skeletal-related events in patients with prostate cancer. Am J Manag Care. 2008;14(5):317-22.
  4. Tchekmedyian NS, Chen YM, Saad F. Disease progression increases the risk of skeletal-related events in patients with bone metastases from castration-resistant prostate cancer, lung cancer, or other solid tumors. Cancer Invest. 2010;28(8):849-55.
  5. Reed SD, Radeva JI, Glendenning GA, Saad F, Schulman KA. Costeffectiveness of zoledronic acid for the prevention of skeletal complicationsin patients with prostate cancer. J Urol. 2004;171(4):1537-42.
  6. Hillner BE, Weeks JC, Desch CE, Smith TJ. Pamidronate in prevention of bone complications in metastatic breast cancer: a cost-effectiveness analysis. J Clin Oncol. 2000;18(1):72-79.

 

 


 Written by:
Jipan Xie, MD, PhD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.


 

 

Economic evaluation of denosumab compared with zoledronic acid in hormone-refractory prostate cancer patients with bone metastases - Abstract

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