The planned interim results of an international, open-label, phase 2 clinical trial published in the Lancet Oncology indicate that Xgeva® (denosumab) is safe and effective in the treatment of giant cell tumor of the bone. In fact, 96 percent of patients with surgically unsalvageable disease had no disease progression after a median follow-up of 13 months.
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 is approved for the prevention of bone complications such as fracture in patients with bone metastases from solid (not blood-related) cancers—and also 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 study included 282 adults or skeletally mature adolescents with histologically confirmed GCTB and radiographically measurable active disease. Patients were divided into three cohorts:
- Cohort 1: Patients with surgically unsalvageable GCTB
- Cohort 2: Patients with salvageable GCTB whose surgery was associated with severe morbidity
- Cohort 3: Patients who transferred from a previous study of Xgeva for GCTB.
Patients in the first two cohorts received 120 mg of subcutaneous Xgeva every 4 weeks with loading doses on days 8 and 15 of the first cycle; those in cohort 3 continued the regimen from the previous study. The primary endpoint of the study was the safety profile of Xgeva. Secondary endpoints included time to disease progression and the proportion of patients without any surgery at six months.
After a median follow-up of 13 months, 96 percent (163 out of 169) of patients in cohort 1—with surgically unsalvageable GCTB—had no disease progression. Among patients in cohort 2—those with salvageable GCTB whose surgery was associated with severe morbidity—74 percent (74 out of 100) of patients required no surgery and 62 percent (16 out of 26) of patients who did have surgery underwent a less morbid procedure than planned. Overall, 72 percent of patients had objective tumor response according to the defined protocol criteria, including 25 percent who had an objective tumor response according to modified RECIST(Response Evaluation Criteria In Solid Tumors).
The researchers found that adverse events were consistent with the known safety profile of Xgeva. One percent (3/281) patients experienced osteonecrosis of the jaw and five percent (15/281) experienced hypocalcemia. The most common grade 3 or 4 adverse events were low phosphate levels, back pain, pain in extremities, musculoskeletal pain, and anemia. Serious adverse events were reported in nine percent (25/281) of patients. No treatment-related deaths were reported.
The researchers concluded that Xgeva represents a new treatment option for patients with GCTB, as it was associated with tumor responses and reduced the need for morbid surgery in patients with the disease.
Chawla S, Henshaw R, Seeger L, et al. Safety and efficacy of denosumab for adults and skeletally mature adolescents with giant cell tumour of bone: interim analysis of an open-label, parallel-group, phase 2 study. The Lancet Oncology. 2013; 9: 901-908.