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document
Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer : a randomized , double-blind study . 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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Intervention_Pharmacological
Denosumab
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Intervention_Pharmacological
zoledronic acid
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Intervention_Pharmacological
denosumab
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Outcome_Physical
delaying time to first on-study SRE
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Outcome_Physical
time to first and subsequent ( multiple ) on-study SREs
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Outcome_Physical
Reduction in bone turnover markers
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Outcome_Mortality
Overall survival
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Outcome_Physical
disease progression
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Outcome_Adverse-effects
rates of adverse events ( AEs ) and serious AEs
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Outcome_Adverse-effects
excess of renal AEs
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Outcome_Adverse-effects
Osteonecrosis of the jaw
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Participant_Condition
advanced breast cancer
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Participant_Condition
breast cancer with bone metastases