Comparing the Value of Denosumab versus Zoledronic Acid in Preventing Cancer-Related Skeletal Events

Caroline Helwick

August 2011, Vol 2, No 5 - ASCO Annual Meeting

Chicago, IL—Two agents are vying to be the preferred option for bone protection in patients with cancer—the blockbuster drug zoledronic acid (ZA; Zometa, Reclast) and the newer drug denosumab (Prolia), which was ap – proved last year for the prevention of skeletal-related events (SREs) in patients with cancer.

Denosumab has proved more effective in preventing SREs than the standard agent, ZA, in several cancer types, but its wholesale acquisition cost per injection is $1650 compared with $886 for ZA. Some oncologists have questioned whether the benefit is worth the cost. At ASCO 2011, studies sponsored by the 2 manufacturers addressed the drugs’ value, but the “winner” is still not clear.

Treatment of Metastatic Breast Cancer

Using a literature-based Markov model, investigators analyzed the survival, quality-adjusted life-years (QALYs), number and costs of SREs, and costs of the 2 drugs in patients with metastatic breast cancer. The conclusion was that denosumab’s cost per QALY far exceeds what is traditionally considered good value.John A. Carter

“This analysis raises questions about the cost/benefit ratio of denosumab in metastatic breast cancer,” said John A. Carter, research analyst, Pharmerit North America, Bethesda, MD.

Inputs were selected to reproduce the phase 3 trial outcomes for as long as 28 months. QALYs were estimated by assigning utilities to health states. SRE-related costs and utilities were obtained from the literature; per-event SRE costs ranged from $4039 (vertebral fracture) to $20,734 (bone surgery). In a sensitivity analysis, serious adverse events (AEs) of $15,441 per patient were included. Scenario analyses were also assessed. All costs and outcomes were discounted at 3% annually.

Compared with ZA, denosumab resulted in fewer SREs, more QALYs, and lower SRE-related costs, but higher drug-related and total costs. This resulted in an incremental cost of $6884 per patient. The cost per QALY gained was $613,000 per QALY when including serious AEs ($644,000 when excluding them).

“Relative to ZA, the use of denosumab for the prevention of SREs in metastatic breast cancer is estimated to reduce SRE-related costs over 28 months of treatment. However, one must invest more than $9000 in additional drug costs and thus incur a net cost of $7000 over 28 months to achieve these benefits,” Mr Carter concluded.

“The resultant cost per QALY…is far above what is traditionally considered to be good value for a medical intervention in the US ($50,000-$100,000 per QALY),” he noted.

Treatment of Castration-Resistant Prostate Cancer

Using the same study design as the breast cancer study, Sonya J. Snedecor, Associate Director of Health Economics, Pharmerit North America, Bethesda, MD, similarly concluded that the cost per QALY of denosumab in men with metastatic castration-resistant prostate cancer (mCRPC) is “far higher than what is considered in the US to be good value for a medical intervention, thus raising questions about the value of using denosumab in mCRPC.”

The use of denosumab was predicted to result in an incremental cost per QALY gained of $1.25 million. The high cost was attributed to denosumab being associated with higher drug acquisition costs, limited prevention of SREs, and no additional overall survival or disease progression benefits versus ZA.

The cost of drug administration and monitoring was figured at $12,963 for ZA and $20,277 for denosumab, Dr Snedecor said.

Low Number Needed to Treat Demonstrates Efficacy

However, in another analysis, investigators found a low number needed to treat (NNT) to prevent 1 SRE. Gary Richardson, MD, of Cabrini Hospital in Malvern, Australia, reported the results of this international randomized double-blind trial.

In this study, denosumab was compared with ZA in 1776 patients with cancer. Results showed that denosu – mab was superior to ZA in preventing SREs and bone metastases and was noninferior when patients with multiple myeloma (MM) were included.

The NNT to prevent the first SRE and the first and subsequent on-study SREs were determined based on data from the initial placebo-controlled trials.

The NNT to prevent 1 additional first SRE during 1 year was 7.8 for denosumab versus ZA and only 3.0 for denosumab versus placebo. For the analysis of time to first and subsequent SREs (ie, multiple SREs), the NNT with denosumab versus ZA was 6.5. When patients with MM were included, the NNT was 9.9 versus ZA and 3.0 versus placebo.

“These low NNT values demonstrate the therapeutic efficacy of denosumab,” Dr Richardson said.