Xgeva® (denosumab) significantly reduced or eliminated tumor giant cells in patients with giant-cell tumor of the bone and also increased new bone formation, according to the results of a phase II study published in Clinical Cancer Research.
Giant cell tumor of bone (GCTB) is a rare, aggressive, benign osteolytic tumor in which bone destruction is mediated by a protein known as the RANK ligand. This protein regulates the activity of osteoclasts (cells that break down bone). GCTB typically affects younger adults between the ages of 20 to 40. Currently, the only treatment option for patients with GCTB is surgery; however, patients who undergo surgery often have recurrent disease or devastating consequences, such as amputation. What’s more—about 25 to 30 percent of patients with GCTB have to undergo joint replacements.
Xgeva is a type of targeted drug known as a monoclonal antibody. The drug targets the RANK ligand, thereby inhibiting bone destruction and potentially eliminating giant cells. Xgeva is approved for the prevention of bone complications such as fracture in patients with bone metastases from solid (not blood-related) cancers. It has also been granted U.S. orphan drug designation for GCTB.
To evaluate the use of Xgeva in the treatment of GCTB, researchers conducted a phase II study that included 20 adult patients with recurrent or unresectable GCTB. All patients received Xgeva injections every four weeks. After treatment, all patients had a 90 percent or greater decrease in giant cells, which indicated a reduction in tumor burden. What’s more—65 percent of patients had new bone growth in areas where the RANK ligand had previously caused bone destruction.
The researchers concluded that Xgeva significantly reduced or eliminated RANK-positive tumor giant cells and increased new bone growth. These results are significant in a disease where radical surgery is typically the only treatment option. Research is ongoing to evaluate the effects of Xgeva in GCTB. Future studies may focus on neoadjuvant (prior to surgery) treatment with Xgeva. Minimizing or avoiding surgery altogether would be a significant development in this disease, especially because joint replacements typically last only 15-20 years before the need for repeat surgery.
Branstetter DG, Nelson SD, Manive JC, et al. Denosumab induces tumor reduction and bone formation in patients with giant-cell tumor of bone. Clinical Cancer Research. 2012; 18: 4415-4424.
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