Bone Turnover Marker (BTM) Changes after Denosumab in Giant Cell Tumors of Bone (GCTB): A Phase II Trial Correlative...

Area of Science:

• Oncology
• Bone Metabolism
• Pharmacodynamics

Background:

• Giant cell tumors of bone (GCTB) are aggressive osteolytic bone lesions.
• Denosumab, a receptor activator of nuclear factor kappa-B ligand (RANK-L) inhibitor, is an established treatment for GCTB.
• Limited data exist on the impact of denosumab on serum bone turnover markers (sBTMs) in GCTB patients.

Purpose of the Study:

• To investigate the changes in sBTMs in GCTB patients treated with denosumab.
• To evaluate the correlation between sBTMs and disease-free survival (DFS) in this patient cohort.
• To identify potential predictive markers for treatment response and disease progression.

Main Methods:

• A multicentre, open-label, phase 2 study enrolled 54 GCTB patients receiving denosumab.
• Serum levels of carboxyterminal-crosslinked-telopeptide of type I collagen (s-CTX), alkaline phosphatase (ALP), bone-alkaline phosphatase (bALP), parathyroid hormone (sPTH), and osteocalcin (OCN) were measured prospectively at baseline and at 3 and 6 months.
• Disease-free survival (DFS) was assessed with a median follow-up of 59 months.

Main Results:

• Denosumab treatment led to a significant reduction in sBTMs, including s-CTX, ALP, bALP, and OCN, with the exception of sPTH.
• The 3-year DFS was 65%. Patients with high baseline s-CTX (≥500 UI/mL) exhibited significantly worse DFS (45%) compared to those with low baseline s-CTX (<500 UI/mL) (75%).
• Elevated median ALP and s-CTX levels were observed in patients with larger tumor size (≥ 5 cm).

Conclusions:

• Denosumab effectively reduces key serum bone turnover markers in GCTB patients.
• Baseline s-CTX levels are a significant predictor of disease progression and DFS in GCTB patients treated with denosumab.
• High baseline s-CTX identifies a subset of patients with a higher risk of disease progression, warranting closer monitoring.