Denosumab Approved by FDA for Giant-Cell Tumor of the Bone

The first treatment for a rare tumor called giant-cell tumor of the bone (GCTB) has been approved by the US Food and Drug Administration (FDA). The approval of denosumab (Xgeva) was based on a priority FDA review.

The therapy is indicated for those adults and adolescents whose bones have fully matured and whose GCTB cannot be removed by surgery or when surgery would remove a substantial part of a limb. This accelerated type of review is a way to offer major advances for diseases that are rare and difficult to treat.

GCTB is a tumor that destroys bone tissue, resulting in fractures, pain, and limited range of motions. The rare disease typically affects those between the ages of 20 and 40. GCTB is generally not malignant-in very rare cases, it does spread to other tissues. The malignant form of GCTB targets the lungs.

Denosumab is already approved for the prevention of fractures and to slow bone metastases in patients with solid tumors. The monoclonal antibody targets the protein RANKL, which is essential to maintain healthy bone tissue. Denosumab inhibits a process called bone resorption executed by bone cells known as osteoclasts.

Denosumab is also marketed as Prolia for the prevention of fractures in postmenopausal women who have osteoporosis. The drug has been studied in men with advanced prostate cancer to prevent or delay the spread of the disease to the bone, but the FDA has asked for more data before the drug could be approved for this indication.

The approval was based on data from 305 adults and adolescents with GCTB who took part in two clinical trials. Twenty-five percent (47 of 187) of patients whose tumors could be measured had a reduction in tumor size after an average of 3 months when treated with denosumab. Over an average of 20 months of follow-up, three patients had regrowth of their tumor after an initial response.

Side effects of denosumab exhibited by patients on the trials included headache, nausea, joint pain, back pain, and pain in the extremities. Serious adverse events included areas of dead bone in the jaw (known as osteonecrosis), and inflammation or infection of the bone (osteomyelitis).