Cleeland, C. S., Body, J. J., Stopeck, A., von Moos, R., Fallowfield, L., Mathias, S. D., . . . Chung, K. (2013). Pain outcomes in patients with advanced breast cancer and bone metastases: results from a randomized, double-blind study of denosumab and zoledronic acid. Cancer, 119, 832–838.

The purpose of this study was to compare the effects of denosumab to those of zoledronic acid on the pain of patients with advanced breast cancer and bone metastases.

Patients were randomly assigned to receive one of two treatments. One group received monthly subcutaneous denosumab 120 mg and intravenous (IV) placebo. The other group received monthly IV intravenous zoledronic acid with standard dosing and adjustments. Investigators assessed pain severity and the extent to which pain interfered with daily function at baseline and monthly.

• The sample included 2,046 patients.
• Mean patient age was 56.5 years.
• All patients were female.
• All patients had breast cancer with bone metastases. Of all patients,15% had no pain at baseline. Average worst pain severity at baseline was less than five in both groups. At baseline, 16% to 17% of all patients were being treated with strong opioids.

• Multi-site
• Outpatient
• Multi-national

• Late effects and survivorship
• Palliative care 

This study was a double-blind, double-dummy, active, randomized, controlled trial.

• Brief Pain Inventory
• Scale measuring pain severity (The authors defined a meaningful change in pain severity as a change equal to or greater than 2.)

The pain of all patients worsened throughout the study. Compared to patients receiving zoledronic acid who had no or mild pain at baseline, fewer denosumab-receiving patients with the same pain profile progressed to severe pain (p = 0.002). Median time to improvement, among patients reporting worst pain, was similar between groups. Median time to decrease in pain was similar between groups, but patients receiving denosumab waited slightly longer for relief.

Fewer patients in the denosumab group progressed to severe pain than did patients in the zoledronic acid group. Patients in the denosumab group took longer to progress to higher levels of pain.

Both denosumab and zoledronic acid have been shown to reduce skeletal events and bone pain in patients with bone metastases. Findings from this study suggest that denosumab may extend the time that patients have before pain progresses to severe levels. Because denosumab does not require IV administration, it may be a practical alternative for some patients.