Denosumab versus zoledronic acid in cases of surgically unsalvageable giant cell tumor of bone: A randomized clinical trial.

BACKGROUND: Although denosumab has been approved as an antiresorptive agent for giant cell tumor of bone, its efficacy has not been proven.

OBJECTIVES: To compare the efficacy and safety of denosumab and zoledronic acid treatment in patients with surgically unsalvageable giant cell tumor of bone.

METHODS: A total of 250 patients with surgically unsalvageable giant cell tumor of bone were included in this randomized clinical trial. Patients received either subcutaneous denosumab (DB group; 120 mg per 4 weeks plus an additional 120 mg on days 8 and 15; n  = 125) or intravenous zoledronic acid (ZA group; 4 mg per 4 weeks; n  = 125) for six cycles. Disease status, clinical benefits, treatment-emergent adverse effects, overall survival, and cost of treatment were evaluated during the follow-up period. Statistical significance was determined using 95% confidence intervals.

RESULTS: Denosumab and zoledronic acid had similar tumor responses ( p  = 0.18) and clinical benefits ( p  = 0.476). Disease progression was observed in fewer patients in the DB group (1%) than ZA group (2%). Denosumab caused fatigue ( p  = 0.0004) and back pain ( p  < 0.0001), while zoledronic acid caused hypocalcemia ( p  < 0.0001), flu-like symptoms ( p  = 0.021), hypotension ( p  = 0.021), and hypokalemia ( p  = 0.021). Denosumab treatment was markedly more expensive than zoledronic acid treatment ( p  < 0.0001). The cost to manage treatment-emergent adverse effects was higher for the ZA group than the DB group ( p  = 0.0425). Overall survival was the same for both treatments ( p  = 0.066).

CONCLUSIONS: Denosumab is a safe but costly alternative to zoledronic acid for treatment of surgically unsalvageable giant cell tumor of bone.