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Case Reports
. 2022 Jul 19:12:953149.
doi: 10.3389/fonc.2022.953149. eCollection 2022.

Rechallenge of denosumab in advanced giant cell tumor of the bone after atypical femur fracture: A case report and review of literature

Vincenzo Nasca  1 , Anna Maria Frezza  1 , Carlo Morosi  2 , Ciriaco Buonomenna  2 , Antonina Parafioriti  3 , Giorgio Zappalà  4 , Federica Bini  5 , Paolo Giovanni Casali  1   6 , Mattia Loppini  7   8 , Silvia Stacchiotti  1
Affiliations
Case Reports

Rechallenge of denosumab in advanced giant cell tumor of the bone after atypical femur fracture: A case report and review of literature

Vincenzo Nasca et al. Front Oncol. .

Abstract

Giant cell tumor of the bone (GCTB) is a locally aggressive neoplasm where surgery is often curative. However, it can rarely give rise to distant metastases. Currently, the only available active therapeutic option for unresectable GCTB is denosumab, an anti-RANKL monoclonal antibody that dampens the aggressive osteolysis typically seen in this disease. For advanced/metastatic GCTB, denosumab should be continued lifelong, and although it is usually well tolerated, important questions may arise about the long-term safety of this drug. In fact, uncommon but severe toxicities can occur and eventually lead to denosumab discontinuation, such as atypical fracture of the femur (AFF). The optimal management of treatment-related AFF is a matter of debate, and to date, it is unknown whether reintroduction of denosumab at disease progression is a clinically feasible option, as no reports have been provided so far. Hereinafter, we present a case of a patient with metastatic GCTB who suffered from AFF after several years of denosumab; we describe the clinical features, orthopedic treatment, and oncological outcomes, finally providing the first evidence that denosumab rechallenge after AFF occurrence may be a safe and viable option at GCTB progression.

Keywords: atypical femur fracture; bone tumor; denosumab; giant cell tumor of bone; sarcoma.

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Conflict of interest statement

AF, PC and SS perceived funds for institutional research and grants from Advenchen Laboratories, Amgen Dompé, AROG Pharmaceuticals, Bayer, Blueprint Medicines, Daiichi Sankyo, Deciphera, Eisai, Eli Lilly, Epizyme Inc, Glaxo, Karyopharm Pharmaceuticals, Novartis, Pfizer, PharmaMar. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Response of target lesion (located in the sacrum) to denosumab in a metastatic giant cell tumor of the bone (GCTB). Left panel’s image is a CT scan showing a sacral lesion at baseline, and, on the right panel, a CT scan after 3 months of denosumab treatment showing a reduction in tumor size (partial response according to RECIST 1.1).
Figure 2
Figure 2
Plain X-ray showing complete, displaced femoral diaphyseal fracture (left panel), reported as an atypical femur fracture (AFF). Patient was treated with open reduction and intramedullary nailing, but bone healing was delayed (plain X-ray after 5 months from surgery, central image). Bony callus eventually fully consolidated after 13 months (right panel).
Figure 3
Figure 3
After 14 months from denosumab discontinuation due to AFF, progressive disease was documented (new lesions in right iliac wing and L5 soma, left panel) and denosumab restarted. On the right panel, a CT scan obtained 3 months later shows stabilization of disease (stable disease according to RECIST 1.1).
Figure 4
Figure 4
Proposed clinical algorithm for the management of AFF during denosumab treatment in unresectable giant cell tumor of bone (GCTB) patients. AFF, atypical femur fracture; SXA, single-energy X-ray absorptiometry.
See this image and copyright information in PMC

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