Dual-target neoadjuvant therapy with denosumab and sunitinib for giant cell tumor of bone: a sarcoma center...

Giant cell tumor of bone (GCTB) is a locally aggressive tumor characterized by osteoclast-like giant cells and neoplastic stromal cells. While denosumab effectively targets giant cells, stromal cells may persist and drive recurrence. This study evaluates the efficacy and safety of a novel neoadjuvant regimen combining denosumab with sunitinib, a tyrosine kinase inhibitor targeting stromal cell signaling. To our knowledge, this represents the first clinical series evaluating a novel neoadjuvant regimen combining denosumab with sunitinib in GCTB.

We conducted a retrospective case series of 16 patients with histologically confirmed Campanacci grade 3 (or grade 2 in anatomically challenging locations) GCTB treated at a tertiary sarcoma center between January 2019 and September 2024. All patients received neoadjuvant denosumab and sunitinib prior to definitive surgery. Surgical outcomes, local recurrence, histopathological tumor regression, disease-free survival, and the relative tyrosine phosphorylation levels were analyzed.

Of the 16 patients (mean age 28.7 years), most had Campanacci grade 3 lesions (87.5%). En-bloc resection was performed in 43.8% and curettage in 50% of cases. Histological analysis showed near-complete regression of giant cells (mean 99.7%) and partial regression of stromal cells (mean 62.8%). Two patients (12.5%) experienced local recurrence. Disease-free survival at two years was 80%. Treatment was well tolerated, with no unexpected adverse events or dose-limiting toxicities.

Neoadjuvant combination therapy with denosumab and sunitinib was feasible and well tolerated and resulted in substantial histological regression of both giant cells and neoplastic stromal cells. While recurrence outcomes in this limited cohort remain descriptive, the observed stromal suppression and RTK signaling profiles support the biological rationale for dual-targeted therapy. These findings justify further prospective investigation, particularly in aggressive or surgically challenging GCTB cases.