Chawla, Lancet Oncol 2013 - Safety and Efficacy of Denosumab for Adults and Skeletally Mature Adolescents with Giant Cell Tumour of Bone: Interim Analysis of an Open-Label, Parallel-Group, Phase 2 Study
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Safety and Efficacy of Denosumab for Adults and Skeletally Mature Adolescents with Giant Cell Tumour of Bone: Interim Analysis of an Open-Label, Parallel-Group, Phase 2 Study
Chawla, Jacobs, et al.·Lancet Oncol·2013·585 citations
Chawla and colleagues reported interim safety and efficacy of denosumab in adults and skeletally mature adolescents with giant cell tumor of bone.
Open‑label phase 2 trial at 29 centers (2008 to 2011) of 282 patients, without a control group, analyzed at an interim cutoff. Funded and co‑designed by the drug's maker.
Key Findings
In unsalvageable disease, 163 of 169 patients (96%) had no investigator‑assessed progression at a median 13 months.
Of 100 patients facing morbid surgery, 74 had no surgery by the cutoff. Of the 26 who did, 16 (62%) had a less morbid procedure than planned, often curettage instead of resection.
Masked central imaging review found an objective response in 136 of 190 patients (72%): 25% by RECIST but 76% by inverse Choi criteria, which count new bone formation.
Osteonecrosis of the jaw occurred in 3 of 281 patients (1%), two after recent tooth extraction, and hypocalcemia in 15 (5%). Serious adverse events affected 25 (9%), with no treatment‑related deaths.
Three patients developed a new malignancy, including one sarcoma thought to be malignant transformation. Investigators judged none related to denosumab.
Disease status, benefit and surgical decisions were judged by unmasked treating physicians. Imaging review was retrospective and omitted 113 patients, mainly for lack of consent or images.
Board pearl
Denosumab works by blocking RANK ligand, which GCTB stromal cells express to activate the osteoclast‑like giant cells. Because responding lesions may ossify rather than shrink, size criteria such as RECIST may understate response.
Authors' conclusion
Adverse events were consistent with the known safety profile of denosumab. Denosumab was associated with tumour responses and reduced the need for morbid surgery in patients with GCTB. Denosumab represents a new treatment option for patients with GCTB.
Safety and Efficacy of Denosumab for Adults and Skeletally Mature Adolescents with Giant Cell Tumour of Bone: Interim Analysis of an Open-Label, Parallel-Group, Phase 2 Study
Chawla, Jacobs, et al.·Lancet Oncol·2013·585 citations
Chawla and colleagues reported interim safety and efficacy of denosumab in adults and skeletally mature adolescents with giant cell tumor of bone.
Open‑label phase 2 trial at 29 centers (2008 to 2011) of 282 patients, without a control group, analyzed at an interim cutoff. Funded and co‑designed by the drug's maker.
Key Findings
In unsalvageable disease, 163 of 169 patients (96%) had no investigator‑assessed progression at a median 13 months.
Of 100 patients facing morbid surgery, 74 had no surgery by the cutoff. Of the 26 who did, 16 (62%) had a less morbid procedure than planned, often curettage instead of resection.
Masked central imaging review found an objective response in 136 of 190 patients (72%): 25% by RECIST but 76% by inverse Choi criteria, which count new bone formation.
Osteonecrosis of the jaw occurred in 3 of 281 patients (1%), two after recent tooth extraction, and hypocalcemia in 15 (5%). Serious adverse events affected 25 (9%), with no treatment‑related deaths.
Three patients developed a new malignancy, including one sarcoma thought to be malignant transformation. Investigators judged none related to denosumab.
Disease status, benefit and surgical decisions were judged by unmasked treating physicians. Imaging review was retrospective and omitted 113 patients, mainly for lack of consent or images.
Board pearl
Denosumab works by blocking RANK ligand, which GCTB stromal cells express to activate the osteoclast‑like giant cells. Because responding lesions may ossify rather than shrink, size criteria such as RECIST may understate response.
Authors' conclusion
Adverse events were consistent with the known safety profile of denosumab. Denosumab was associated with tumour responses and reduced the need for morbid surgery in patients with GCTB. Denosumab represents a new treatment option for patients with GCTB.