Surgical downstaging in an open-label phase II trial of denosumab in patients with giant cell tumor of bone

Piotr Rutkowski, Stefano Ferrari, Robert J Grimer, Paul D Stalley, Sander P D Dijkstra, Andrzej Pienkowski, Gualter Vaz, Jay S Wunder, Leanne L Seeger, Amy Feng, Zachary J Roberts, Bruce A Bach, Piotr Rutkowski, Stefano Ferrari, Robert J Grimer, Paul D Stalley, Sander P D Dijkstra, Andrzej Pienkowski, Gualter Vaz, Jay S Wunder, Leanne L Seeger, Amy Feng, Zachary J Roberts, Bruce A Bach

Abstract

Background: Surgical resection with curative intent for giant cell tumor of bone (GCTB) may be associated with severe morbidity. This interim analysis evaluated reduction in surgical invasiveness after denosumab treatment in patients with resectable GCTB.

Methods: Patients with primary or recurrent GCTB, for whom the initially planned surgery was associated with functional compromise or morbidity, received denosumab 120 mg subcutaneously every 4 weeks (additional doses on days 8 and 15 of the first cycle). Planned and actual GCTB-related surgical procedures before and after denosumab treatment were reported. Patients were followed for surgical outcome, adverse events, and recurrence following resection.

Results: Overall, 222 patients were evaluable for surgical downstaging (54 % were women; median age 34 years). Lesions (67 % primary and 33 % recurrent) were located in the axial (15 %) and appendicular skeleton (85 %). At the data cutoff date, most patients had not yet undergone surgery (n = 106; 48 %) or had a less morbid procedure (n = 84; 38 %) than originally planned. Median (interquartile range) time on denosumab was 19.5 (12.4-28.6) months for the 106 patients who had not undergone surgery and were continuing on monthly denosumab. Native joint preservation was 96 % (n = 24/25) for patients with planned joint/prosthesis replacement and 86 % (n = 30/35) for patients with planned joint resection/fusion. Of the 116 patients who had surgery (median postsurgical follow-up 13.0 [8.5-17.9] months), local recurrence occurred in 17 (15 %) patients.

Conclusion: For patients with resectable GCTB, neoadjuvant denosumab therapy resulted in beneficial surgical downstaging, including either no surgery or a less morbid surgical procedure.

Figures

Fig. 1
Fig. 1
Giant cell tumor of bone lesion location at baseline and operative status. Lesion locations highlighted in blue show sites where ≥50 % of patients remain on denosumab without curative intent surgery
Fig. 2
Fig. 2
Example of radiographic images of giant cell tumor of bone of the proximal humerus and distal femur before (a, c) and after (b, d) denosumab therapy. The initial lesions were expansile with a thin peripheral calcified shell and primarily soft tissue density centrally (a) and showed extensive soft tissue displacement with progression following radiotherapy 2 years previously (c). After 4 months of treatment with denosumab, the peripheral calcification was thicker, the central lesion more heavily mineralized, and the overall size was slightly decreased (b, d)

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Source: PubMed

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