Researchers involved in an international Phase II clinical trial have reported that 86% of patients with giant cell tumor of the bone responded to treatment with denosumab. These results were presented at the 2009 annual meeting of the American Society of Clinical Oncology in Orlando, Florida, on June 1.

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

Giant cell tumor of the bone is a relatively uncommon bone tumor. In most patients it does not spread to other parts of the body, but it can cause extensive local destruction of bone if not effectively treated. These tumors tend to be rich in cells that express the RANK ligand, suggesting a possible role for denosumab in the treatment of this condition.

To evaluate the effect of denosumab among patients with giant cell tumor of the bone, researchers conducted a Phase II clinical trial among 37 patients with measurable or unresectable tumors. All patients were treated with denosumab.

The primary outcome of interest was tumor response. This was defined as at least 90% elimination of giant cells or no radiographic progression of the tumor. Tumor response was assessed at week 25 of the study.

• 86% of patients showed evidence of tumor response.
• 84% of patients reported reduced pain or improvement in functional status.
• Side effects were reported by 89% of patients, but no serious treatment-related side effects occurred.

Comments: This study suggests that denosumab produces a high rate of tumor response in patients with giant cell tumor of the bone. Additional studies of denosumab for the treatment of this condition are warranted.

Reference: Thomas DM, Chawla S, Skubitz K et al. Denosumab for the treatment of giant cell tumor (GCT) of bone: final results from a proof-of-concept, phase II study. Presented at the 2009 annual meeting of the American Society of Clinical Oncology, May 29-June 2, 2009, Orlando, FL. Abstract 10510.