PMID- 21060033
OWN - NLM
STAT- MEDLINE
DCOM- 20110120
LR  - 20220408
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Linking)
VI  - 28
IP  - 35
DP  - 2010 Dec 10
TI  - Denosumab compared with zoledronic acid for the treatment of bone metastases in 
      patients with advanced breast cancer: a randomized, double-blind study.
PG  - 5132-9
LID - 10.1200/JCO.2010.29.7101 [doi]
AB  - PURPOSE: This randomized study compared denosumab, a fully human monoclonal 
      antibody against receptor activator of nuclear factor kappa 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.
FAU - Stopeck, Alison T
AU  - Stopeck AT
AD  - University of Arizona, Arizona Cancer Center, Tucson, AZ, USA. 
      astopeck@azcc.arizona.edu
FAU - Lipton, Allan
AU  - Lipton A
FAU - Body, Jean-Jacques
AU  - Body JJ
FAU - Steger, Guenther G
AU  - Steger GG
FAU - Tonkin, Katia
AU  - Tonkin K
FAU - de Boer, Richard H
AU  - de Boer RH
FAU - Lichinitser, Mikhail
AU  - Lichinitser M
FAU - Fujiwara, Yasuhiro
AU  - Fujiwara Y
FAU - Yardley, Denise A
AU  - Yardley DA
FAU - Viniegra, Maria
AU  - Viniegra M
FAU - Fan, Michelle
AU  - Fan M
FAU - Jiang, Qi
AU  - Jiang Q
FAU - Dansey, Roger
AU  - Dansey R
FAU - Jun, Susie
AU  - Jun S
FAU - Braun, Ada
AU  - Braun A
LA  - eng
SI  - ClinicalTrials.gov/NCT00321464
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20101108
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Bone Density Conservation Agents)
RN  - 0 (Diphosphonates)
RN  - 0 (Imidazoles)
RN  - 0 (RANK Ligand)
RN  - 4EQZ6YO2HI (Denosumab)
RN  - 6XC1PAD3KF (Zoledronic Acid)
SB  - IM
CIN - J Clin Oncol. 2010 Dec 10;28(35):5127-31. PMID: 21060038
CIN - Future Oncol. 2011 Mar;7(3):381-3. PMID: 21417901
CIN - J Clin Oncol. 2011 May 10;29(14):e419-20; author reply e421-4. PMID: 21464408
CIN - J Clin Oncol. 2011 Jun 10;29(17):e521-2; author reply e523-4. PMID: 21537047
MH  - Aged
MH  - Antibodies, Monoclonal/*therapeutic use
MH  - Antibodies, Monoclonal, Humanized
MH  - Bone Density Conservation Agents/*therapeutic use
MH  - Bone Diseases/etiology/*prevention & control
MH  - Bone Neoplasms/complications/*drug therapy/secondary
MH  - Bone and Bones/drug effects
MH  - Breast Neoplasms/*pathology
MH  - Denosumab
MH  - Diphosphonates/*therapeutic use
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Imidazoles/*therapeutic use
MH  - Middle Aged
MH  - RANK Ligand/*therapeutic use
MH  - Zoledronic Acid
EDAT- 2010/11/10 06:00
MHDA- 2011/01/21 06:00
CRDT- 2010/11/10 06:00
PHST- 2010/11/10 06:00 [entrez]
PHST- 2010/11/10 06:00 [pubmed]
PHST- 2011/01/21 06:00 [medline]
AID - JCO.2010.29.7101 [pii]
AID - 10.1200/JCO.2010.29.7101 [doi]
PST - ppublish
SO  - J Clin Oncol. 2010 Dec 10;28(35):5132-9. doi: 10.1200/JCO.2010.29.7101. Epub 2010 
      Nov 8.