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

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Simple SummaryGiant cell tumors of bone (GCTB) are a histologically benign, yet often aggressive, skeletal tumor. Surgery is the only potentially curative treatment option, but may be associated with severe morbidity and loss of function. Denosumab, a monoclonal antibody directed to RANK ligand, is approved for GCTB treatment. Here we report the results of a phase II correlative study on sBTMs (carboxytermnal-crosslinked-telopeptide of type I collagen (s-CTX), alkaline phosphatase (ALP), bone-alkaline phosphatase (bALP), parathyroid hormone (sPTH), and osteocalcin (OCN) in GCTB patients treated with denosumab. The main finding of the present research is that the use of denosumab in patients with GCTB induces the bALP/ALP/OCN and s-CTX reduction, with a concomitant increase in sPTH. High baseline s-CTX identifies a group of patients at higher risk of progression of the disease. Stratification of the GCTB patients based on s-CTX might guide type of surgery and follow-up.Background: Giant cell tumors of bone (GCTB) are osteolytic tumors. Denosumab, a RANK-L inhibitor, is approved for GCTB. Data on serum bone turnover marker (sBTM) changes are lacking. We present a phase II correlative study on sBTMs in GCTB patients treated with denosumab. Methods: All GCTB patients receiving denosumab within a multicentre, open-label, phase 2 study were enrolled. 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 prospectively assessed (baseline, T0, 3 months, T1, 6 months, T2). The primary endpoint was assessment of sBTM changes after denosumab; the secondary endpoints were disease-free survival (DFS) and sBTM correlation. Results: In 54 cases, sBTMs decreased during denosumab treatment except for sPTH. With a median follow-up of 59 months, 3-year DFS was 65% (%CI 52–79), with a significantly worse outcome for patients with high (≥500 UI/mL) s-CTX at baseline, as compared to low s-CTX (<500 UI/mL) (3-year DFS for high CTX 45% (95%CI 23–67) vs. 75% (95%CI 59–91) for low s-CTX. Higher median ALP and s-CTX were found for patients with tumor size ≥ 5 cm (p = 0.0512; p = 0.0589). Conclusion: Denosumab induces ALP/OCN and s-CTX reduction. High baseline s-CTX identifies a group of patients at higher risk of progression of the disease.