Denosumab Treatment for Giant Cell Tumor of the Spine Including the Sacrum

• Published in: Spine (Philadelphia, Pa. 1976) Pa. 1976), 2021-03, Vol.46 (5), p.277-284
• Main Authors: Bukata, Susan V., Blay, Jean-Yves, Rutkowski, Piotr, Skubitz, Keith, Henshaw, Robert, Seeger, Leanne, Dai, Tian, Jandial, Danielle, Chawla, Sant
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Bone Density Conservation Agents - therapeutic use; Bone Neoplasms - surgery; Cohort Studies; Combined Modality Therapy - methods; Denosumab - therapeutic use; Female; Giant Cell Tumor of Bone - diagnostic imaging; Giant Cell Tumor of Bone - drug therapy; Giant Cell Tumor of Bone - surgery; Humans; Male; Middle Aged; Randomized Trial; Sacrum - diagnostic imaging; Sacrum - surgery; Spinal Neoplasms - diagnostic imaging; Spinal Neoplasms - drug therapy; Spinal Neoplasms - surgery; Spine - diagnostic imaging; Spine - surgery; Treatment Outcome; Young Adult
• ISSN: 0362-2436; 1528-1159
• DOI: 10.1097/BRS.0000000000003728

STUDY DESIGN.This was a subanalysis of an international, multicenter, open-label study. OBJECTIVE.To assess the efficacy and safety of denosumab in a subset of patients with giant cell tumors of bone (GCTB) of the spine including the sacrum from an international, open-label, single-arm, phase 2 study (ClinicalTrials.govNCT00680992). SUMMARY OF BACKGROUND DATA.Standard GCTB treatment is surgical removal, either by curettage or resection, combined with intraoperative adjuvant therapy; however, some sites may not be amenable to resection (eg, skull, spine). METHODS.Adults or skeletally mature adolescents with pathologically confirmed GCTB of the spine including the sacrum, and radiologically measurable evidence of active disease, were included. Patients received denosumab (120 mg subcutaneously) once every 4 weeks during the treatment phase, with loading doses on days 8 and 15 of the first cycle. Patients had surgically unsalvageable GCTB (Cohort 1), had planned surgery expected to result in severe morbidity (Cohort 2), or were enrolled from a previous GCTB study (Cohort 3). RESULTS.Overall, 132 patients were included in the safety analysis (103 in Cohort 1, 24 in Cohort 2, and 5 in Cohort 3); 131 patients were included in the efficacy analysis. Kaplan-Meier estimated probabilities of disease progression or recurrence were 3% (95% CI, 0.0–6.2) at year 1 and 7.4% (95% CI, 2.1–12.7) at years 3 and 5 in Cohort 1, and not estimable in Cohorts 2 and 3. Of 23 patients (Cohort 2) with surgery planned at baseline, 10 (43%) had on-study surgery; of these one patient had reported disease progression or recurrence after the on-study surgery. Clinical benefit was reported in 83% of patients overall (all cohorts). CONCLUSIONS.Results from the analysis suggest that denosumab is potentially effective treatment for patients with GCTB of the spine including the sacrum. The adverse event profile was consistent with the full study population.Level of Evidence2