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

BACKGROUND: Giant-cell tumor of bone (GCTB) is a relatively benign, but locally aggressive osteoclastogenic stromal tumour of the bone. Although denosumab has been approved as an monoclonal antibody against RANK ligand for the treatment of GCTB, few clinical trials of the benefit in tumor response have been conducted to prove the efficiency in Chinese population. OBJECTIVES: In this multicentric, random controlled, clinical trial, 160 patients were enrolled to compare the therapeutic efficacy and safety of denosumab and zoledronic acid treatment in patients with surgically unsalvageable GCTB. METHODS: Between 2nd Jan 2015 and 1st Jan 2018, 160 adults (aged ≥ 18 years) with ①surgically unsalvageable GCTB, ②surgically salvageable GCTB with planned surgery expected to result in severe morbidity were included in this randomized clinical trial. Patients received either subcutaneous denosumab (DB group; 120 mg once every 4 weeks with loading doses of 120 mg subcutaneously admininstered on days 8 and 15; n = 80) or intravenous zoledronic acid (ZA group; 4 mg once every 4 weeks; n = 80) 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 = 0.118) and clinical benefits (p = 0.574). Disease progression was observed in fewer patients in the DB group (12.5%) than ZA group (15.0%). Denosumab caused fatigue (p = 0.001) and back pain (p < 0.0001), while zoledronic acid caused hypocalcemia (p < 0.0001), flu-like symptoms (p = 0.059) and hypotension (p = 0.059). Denosumab treatment was markedly more expensive than zoledronic acid treatment (p < 0.0001). The cost to manage treatment-emergent adverse effects was the same for the ZA group and the DB group (p = 0.425). The accumulate recurrence-free survival rate at 4-year follow-up is higher in DB group (p = 0.035). CONCLUSIONS: Denosumab is a safe but costly alternative to zoledronic acid for treatment of surgically unsalvageable GCTB.