Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: A randomized, double-blind study

Alison T Stopeck, Allan Lipton, Jean Jacques Body, Guenther G. Steger, Katia Tonkin, Richard H. De Boer, Mikhail Lichinitser, Yasuhiro Fujiwara, Denise A. Yardley, María Viniegra, Michelle Fan, Qi Jiang, Roger Dansey, Susie Jun, Ada Braun

Research output: Contribution to journalArticle

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Abstract

Purpose: This randomized study compared denosumab, a fully human monoclonal antibody against receptor activator of nuclear factor κ B (RANK) ligand, with zoledronic acid in delaying or preventing skeletal-related events (SREs) in patients with breast cancer with bone metastases. Patients and Methods: Patients were randomly assigned to receive either subcutaneous denosumab 120 mg and intravenous placebo (n = 1,026) or intravenous zoledronic acid 4 mg adjusted for creatinine clearance and subcutaneous placebo (n = 1,020) every 4 weeks. All patients were strongly recommended to take daily calcium and vitamin D supplements. The primary end point was time to first on-study SRE (defined as pathologic fracture, radiation or surgery to bone, or spinal cord compression). Results: Denosumab was superior to zoledronic acid in delaying time to first on-study SRE (hazard ratio, 0.82; 95% CI, 0.71 to 0.95; P = .01 superiority) and time to first and subsequent (multiple) on-study SREs (rate ratio, 0.77; 95% CI, 0.66 to 0.89; P = .001). Reduction in bone turnover markers was greater with denosumab. Overall survival, disease progression, and rates of adverse events (AEs) and serious AEs were similar between groups. An excess of renal AEs and acute-phase reactions occurred with zoledronic acid; hypocalcemia occurred more frequently with denosumab. Osteonecrosis of the jaw occurred infrequently (2.0%, denosumab; 1.4%, zoledronic acid; P = .39). Conclusion: Denosumab was superior to zoledronic acid in delaying or preventing SREs in patients with breast cancer metastatic to bone and was generally well tolerated. With the convenience of a subcutaneous injection and no requirement for renal monitoring, denosumab represents a potential treatment option for patients with bone metastases.

Original languageEnglish (US)
Pages (from-to)5132-5139
Number of pages8
JournalJournal of Clinical Oncology
Volume28
Issue number35
DOIs
StatePublished - Dec 10 2010
Externally publishedYes

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zoledronic acid
Double-Blind Method
Breast Neoplasms
Neoplasm Metastasis
Bone and Bones
Therapeutics
Placebos
RANK Ligand
Kidney
Bone Neoplasms
Spontaneous Fractures
Spinal Cord Compression
Acute-Phase Reaction
Osteonecrosis
Hypocalcemia
Denosumab
Bone Remodeling
Subcutaneous Injections
Cytoplasmic and Nuclear Receptors
Jaw

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer : A randomized, double-blind study. / Stopeck, Alison T; Lipton, Allan; Body, Jean Jacques; Steger, Guenther G.; Tonkin, Katia; De Boer, Richard H.; Lichinitser, Mikhail; Fujiwara, Yasuhiro; Yardley, Denise A.; Viniegra, María; Fan, Michelle; Jiang, Qi; Dansey, Roger; Jun, Susie; Braun, Ada.

In: Journal of Clinical Oncology, Vol. 28, No. 35, 10.12.2010, p. 5132-5139.

Research output: Contribution to journalArticle

Stopeck, AT, Lipton, A, Body, JJ, Steger, GG, Tonkin, K, De Boer, RH, Lichinitser, M, Fujiwara, Y, Yardley, DA, Viniegra, M, Fan, M, Jiang, Q, Dansey, R, Jun, S & Braun, A 2010, 'Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: A randomized, double-blind study', Journal of Clinical Oncology, vol. 28, no. 35, pp. 5132-5139. https://doi.org/10.1200/JCO.2010.29.7101
Stopeck, Alison T ; Lipton, Allan ; Body, Jean Jacques ; Steger, Guenther G. ; Tonkin, Katia ; De Boer, Richard H. ; Lichinitser, Mikhail ; Fujiwara, Yasuhiro ; Yardley, Denise A. ; Viniegra, María ; Fan, Michelle ; Jiang, Qi ; Dansey, Roger ; Jun, Susie ; Braun, Ada. / Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer : A randomized, double-blind study. In: Journal of Clinical Oncology. 2010 ; Vol. 28, No. 35. pp. 5132-5139.
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abstract = "Purpose: This randomized study compared denosumab, a fully human monoclonal antibody against receptor activator of nuclear factor κ B (RANK) ligand, with zoledronic acid in delaying or preventing skeletal-related events (SREs) in patients with breast cancer with bone metastases. Patients and Methods: Patients were randomly assigned to receive either subcutaneous denosumab 120 mg and intravenous placebo (n = 1,026) or intravenous zoledronic acid 4 mg adjusted for creatinine clearance and subcutaneous placebo (n = 1,020) every 4 weeks. All patients were strongly recommended to take daily calcium and vitamin D supplements. The primary end point was time to first on-study SRE (defined as pathologic fracture, radiation or surgery to bone, or spinal cord compression). Results: Denosumab was superior to zoledronic acid in delaying time to first on-study SRE (hazard ratio, 0.82; 95{\%} CI, 0.71 to 0.95; P = .01 superiority) and time to first and subsequent (multiple) on-study SREs (rate ratio, 0.77; 95{\%} CI, 0.66 to 0.89; P = .001). Reduction in bone turnover markers was greater with denosumab. Overall survival, disease progression, and rates of adverse events (AEs) and serious AEs were similar between groups. An excess of renal AEs and acute-phase reactions occurred with zoledronic acid; hypocalcemia occurred more frequently with denosumab. Osteonecrosis of the jaw occurred infrequently (2.0{\%}, denosumab; 1.4{\%}, zoledronic acid; P = .39). Conclusion: Denosumab was superior to zoledronic acid in delaying or preventing SREs in patients with breast cancer metastatic to bone and was generally well tolerated. With the convenience of a subcutaneous injection and no requirement for renal monitoring, denosumab represents a potential treatment option for patients with bone metastases.",
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T1 - Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer

T2 - A randomized, double-blind study

AU - Stopeck, Alison T

AU - Lipton, Allan

AU - Body, Jean Jacques

AU - Steger, Guenther G.

AU - Tonkin, Katia

AU - De Boer, Richard H.

AU - Lichinitser, Mikhail

AU - Fujiwara, Yasuhiro

AU - Yardley, Denise A.

AU - Viniegra, María

AU - Fan, Michelle

AU - Jiang, Qi

AU - Dansey, Roger

AU - Jun, Susie

AU - Braun, Ada

PY - 2010/12/10

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N2 - Purpose: This randomized study compared denosumab, a fully human monoclonal antibody against receptor activator of nuclear factor κ B (RANK) ligand, with zoledronic acid in delaying or preventing skeletal-related events (SREs) in patients with breast cancer with bone metastases. Patients and Methods: Patients were randomly assigned to receive either subcutaneous denosumab 120 mg and intravenous placebo (n = 1,026) or intravenous zoledronic acid 4 mg adjusted for creatinine clearance and subcutaneous placebo (n = 1,020) every 4 weeks. All patients were strongly recommended to take daily calcium and vitamin D supplements. The primary end point was time to first on-study SRE (defined as pathologic fracture, radiation or surgery to bone, or spinal cord compression). Results: Denosumab was superior to zoledronic acid in delaying time to first on-study SRE (hazard ratio, 0.82; 95% CI, 0.71 to 0.95; P = .01 superiority) and time to first and subsequent (multiple) on-study SREs (rate ratio, 0.77; 95% CI, 0.66 to 0.89; P = .001). Reduction in bone turnover markers was greater with denosumab. Overall survival, disease progression, and rates of adverse events (AEs) and serious AEs were similar between groups. An excess of renal AEs and acute-phase reactions occurred with zoledronic acid; hypocalcemia occurred more frequently with denosumab. Osteonecrosis of the jaw occurred infrequently (2.0%, denosumab; 1.4%, zoledronic acid; P = .39). Conclusion: Denosumab was superior to zoledronic acid in delaying or preventing SREs in patients with breast cancer metastatic to bone and was generally well tolerated. With the convenience of a subcutaneous injection and no requirement for renal monitoring, denosumab represents a potential treatment option for patients with bone metastases.

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