Efficacy and safety of denosumab de-escalation in giant cell tumor of bone

Abstract Purpose This study aims to investigate the efficacy and safety of denosumab de-escalation for giant cell tumor of bone (GCTB). Methods The medical records of nine patients with unresectable or resectable GCTB not eligible for resection who received de-escalated denosumab treatment at a single institution in 2014–2022 were retrospectively reviewed. The denosumab treatment interval was gradually extended to every 8, 12, and 24 weeks. The radiographic changes and clinical symptoms during standard and de-escalated denosumab therapy were assessed. Results The denosumab interval was de-escalated after a median of 12 months of a standard 4-weekly treatment. Imaging showed that the good therapeutic responses obtained with the 4-weekly treatment were sustained with 8- and 12-weekly treatments. GCTB treated with de-escalated denosumab therapy resulted in a complete and partial responses in one and eight patients, respectively, which were achieved with standard treatment. One patient with small femoral lesion and two patients with sacral lesion proceeded to 24-weekly treatment. Although the patient with femoral lesion had stable disease, both sacral lesions experienced tumor regrowth within 12 months. The extraskeletal masses reduced significantly with standard treatment, while tumor reduction was sustained during de-escalated treatment. The clinical symptoms improved significantly with standard treatment and remained improved during de-escalated treatment. Two patients experienced ONJ and one patient developed malignant transformation. Conclusion In conclusion, 12-weekly de-escalated denosumab treatment showed clinical benefits as a maintenance treatment in patients with unresectable GCTB, in addition to sustained stable tumor control and improved clinical symptoms with standard treatment.