Denosumab Shows Benefit in Patients with Bone Metastases and Prior Bisphosphonate Therapy

Among patients with bone metastases and high levels of bone resorption in spite of treatment with a bisphosphonate drug, bone resorption was reduced to a greater extent among those treated with the investigational drug denosumab than among those who continued bisphosphonate therapy. The results of this Phase II clinical trial were published in the Journal of Clinical Oncology.

Denosumab is an investigational drug that targets a protein known as the RANK ligand. This protein regulates the activity of osteoclasts (cells that break down bone). Denosumab is being studied across a range of conditions, including osteoporosis, treatment-induced bone loss, rheumatoid arthritis, bone metastases, and multiple myeloma. An application was recently submitted to the FDA for use of denosumab in the treatment and prevention of postmenopausal osteoporosis in women and the treatment and prevention of bone loss among patients undergoing hormonal therapy for breast or prostate cancer.

Bisphosphonates are another class of drugs that may be used to treat bone loss or bone metastases. Among patients with bone metastases, some continue to have high levels of bone resorption in spite of treatment with a bisphosphonate drug. These patients are more likely than patients with low levels of bone resorption to experience problems such as bone fracture and progression of bone lesions.[1] A commonly used measure of bone resorption is urinary N-telopeptide (uNTx). Higher levels of uNTx indicate higher
bone resorption.

To evaluate the effects of denosumab among patients with metastatic cancer and high levels of bone resorption in spite of bisphosphonate treatment, researchers in North America and Europe conducted a Phase II clinical trial.[2] The trial enrolled 111 patients, most of whom had breast or prostate cancer. Study participants were assigned to either continue with bisphosphonate therapy or receive denosumab.

The primary objective of the study was to determine whether denosumab reduced
bone resorption (as measured by uNTx) to a greater extent than continued
bisphosphonate therapy.

• A low level of bone resorption was achieved by 71% of patients treated with denosumab compared with 29% of patients who continued with bisphosphonate therapy.
• Skeletal problems such as fracture occurred in 8% of patients treated with denosumab and 17% of patients who continued with bisphosphonate therapy. This difference between groups was not statistically significant, suggesting that it could have occurred by chance alone.

The results of this study suggest that denosumab may benefit patients with bone metastases and high levels of bone resorption in spite of bisphosphonate therapy.

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