Denosumab treatment of giant cell tumor of bone: Interim analysis of an open-label phase II study

Abstract

10500 Background: Giant cell tumor (GCT) of bone is a benign, locally aggressive osteolytic neoplasm that is associated with significant skeletal morbidity and can be lethal. GCT is rich in RANKL, a key mediator of osteoclast formation, function, and survival, suggesting a role for the RANK pathway in the pathogenesis of GCT and a potential therapeutic effect on tumor growth from denosumab, a fully human monoclonal antibody against RANKL. Methods: Patients were adults with resectable or unresectable GCT. Denosumab 120 mg was administered subcutaneously once monthly with loading doses on days 8 and 15 of month 1. The primary endpoint was tumor response (elimination of ≥90% of giant cells or no radiographic progression of the target lesion) at week 25. Of 35 patients enrolled, 25 were eligible for this interim analysis, 24 received denosumab, and 15 were evaluable for efficacy based on available pre- and post-treatment radiology or histology assessments. Results: Thirteen of 15 patients (87%) had a tumor response: 9 of 9 had a histologic response, and 4 of 6 had a radiographic response. The 2 patients who did not meet radiographic response criteria had stable disease per investigators. Substantial clinical benefit was reported in 9 patients, including reduced pain, increased range of motion, and return to work. Evidence of bone repair was reported in 3 patients. Adverse events (AEs) were reported in 19 patients. One death from disease progression (not treatment-related) occurred during follow-up. No treatment-related serious AEs or neutralizing anti-denosumab antibodies were reported. Conclusions: In this analysis, 87% of patients with recurrent or unresectable GCT responded to denosumab treatment. Further investigation of denosumab as a new therapy for GCT is warranted. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen Inc. Amgen, GlaxoSmithKline, Novartis, Pfizer, PharmaMar Amgen Inc. GlaxoSmithKline, Novartis, Pfizer, PharmaMar Amgen, Novartis Amgen Inc.