The U.S. Food and Drug Administration (FDA) has expanded the approved use of Xgeva® (denosumab) to include the treatment of adults and some adolescents with giant cell tumor of the bone (GCTB).
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. Historically, the only treatment option for patients with GCTB has been 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 was approved in 2010 for the prevention of bone complications such as fracture in patients with bone metastases from solid (not blood-related) cancers—and now for patients whose GCTB cannot be surgically removed or for when surgery is likely to result in severe morbidity, such as loss of limb or joint removal.
The expanded approval was the result of two clinical trials that included a total of 305 adult or adolescent patients, all of whom had recurrent or unresectable GCTB or GCTB where surgery would result in severe morbidity. Xgeva was shown to reduce tumor size—of 187 patients with measurable tumors, 47 patients experienced tumor reduction after an average of three months. After an average follow-up of 20 months, three patients whose tumors shrunk during treatment experienced regrowth.
Common side effects included joint pain (arthralgia), headache, nausea, fatigue, back pain and extremity pain. The most common serious side effects were osteonecrosis (areas of dead bone) of the jaw and osteomyelitis (inflammation or infection of the bone).
Xgeva was approved as part of the FDA’s priority review program, which allows an expedited six-month review of drugs that may offer major advances in treatment. The drug should only be used in adolescents whose bones have matured. Women in the reproductive years should take care to use effective contraception while taking Xgeva to prevent potential fetal harm.
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.
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.
- FDA approves Xgeva to treat giant cell tumor of the bone. [FDA News Release]. U.S. Food and Drug Administration website. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm356528.htm
- 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.
- Thomas D, Henshaw R, Skubitz K et al. Denosumab in patients with giant-cell tumor of bone: an open-label, phase 2 study. Lancet Oncology [early online publication]. February 10, 2010.