PMID- 26122727
OWN - NLM
STAT- MEDLINE
DCOM- 20160818
LR  - 20220330
IS  - 1569-8041 (Electronic)
IS  - 0923-7534 (Linking)
VI  - 26
IP  - 11
DP  - 2015 Nov
TI  - Should de-escalation of bone-targeting agents be standard of care for patients 
      with bone metastases from breast cancer? A systematic review and meta-analysis.
PG  - 2205-13
LID - 10.1093/annonc/mdv284 [doi]
AB  - BACKGROUND: De-escalation of bone-targeted agents, such as bisphosphonates and 
      denosumab, from 4- to 12-weekly dosing is an increasingly used strategy in 
      patients with bone metastases from breast cancer. It is unclear whether there is 
      sufficient evidence to support de-escalation as a standard of care. METHODS: A 
      systematic review of randomized trials comparing standard 4-weekly administration 
      of bone-targeted agents with de-escalated (Q12-weekly) dosing in breast cancer 
      patients was carried out. Medline, PubMed and the Cochrane Register of Controlled 
      Trials were searched from inception until November 2014 for relevant studies. 
      Outcomes of interest included skeletal-related event (SRE) rates, bone pain, 
      adverse events (AEs) and bone turnover biomarkers. Random-effects meta-analyses 
      were carried out. RESULTS: A total of nine citations representing seven unique 
      studies were eligible. One study is ongoing with no reported data. Six studies 
      reported data for at least one outcome of interest. Data were available comparing 
      standard versus de-escalated therapy for pamidronate (1 study, 38 patients), 
      zoledronate (3 studies, 1117 patients) and denosumab (2 studies, 284 patients). 
      Meta-analysis of five trials reporting data for on-study SRE rates between 
      standard (61/443 patients) and de-escalated (49/392 patients) arms produced a 
      summary risk ratio of 0.90 (95% confidence interval 0.63-1.29). Meta-analyses of 
      data for AEs and bone turnover biomarkers also showed no statistically 
      significant differences between standard and de-escalated arms, though only 
      limited numbers of patients and events were present for most analyses. 
      CONCLUSION: In this systematic review of studies of bisphosphonates and 
      denosumab, there appears to be no difference in SREs or pain with de-escalated 
      therapy. While a large, hopefully definitive study is ongoing, the data presented 
      so far are consistent with de-escalation of bone-targeting agents becoming a 
      standard of care for patients with bone metastases from breast cancer.
CI  - (c) The Author 2015. Published by Oxford University Press on behalf of the European 
      Society for Medical Oncology. All rights reserved. For permissions, please email: 
      journals.permissions@oup.com.
FAU - Ibrahim, M F K
AU  - Ibrahim MF
AD  - Department of Medicine and Division of Medical Oncology, The Ottawa Hospital.
FAU - Mazzarello, S
AU  - Mazzarello S
AD  - Ottawa Hospital Research Institute and Department of Medicine, University of 
      Ottawa.
FAU - Shorr, R
AU  - Shorr R
AD  - The Ottawa General Hospital, Ottawa, Canada.
FAU - Vandermeer, L
AU  - Vandermeer L
AD  - Ottawa Hospital Research Institute and Department of Medicine, University of 
      Ottawa.
FAU - Jacobs, C
AU  - Jacobs C
AD  - Department of Medicine and Division of Medical Oncology, The Ottawa Hospital.
FAU - Hilton, J
AU  - Hilton J
AD  - Department of Medicine and Division of Medical Oncology, The Ottawa Hospital 
      Ottawa Hospital Research Institute and Department of Medicine, University of 
      Ottawa.
FAU - Hutton, B
AU  - Hutton B
AD  - Ottawa Hospital Research Institute and Department of Medicine, University of 
      Ottawa.
FAU - Clemons, M
AU  - Clemons M
AD  - Department of Medicine and Division of Medical Oncology, The Ottawa Hospital 
      Ottawa Hospital Research Institute and Department of Medicine, University of 
      Ottawa mclemons@toh.on.ca.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Review
PT  - Systematic Review
DEP - 20150628
PL  - England
TA  - Ann Oncol
JT  - Annals of oncology : official journal of the European Society for Medical 
      Oncology
JID - 9007735
RN  - 0 (Bone Density Conservation Agents)
SB  - IM
CIN - Ann Oncol. 2018 May 1;29(5):1333-1334. PMID: 29529190
CIN - Ann Oncol. 2018 May 1;29(5):1329-1330. PMID: 29788163
MH  - Bone Density Conservation Agents/*administration & dosage
MH  - Bone Neoplasms/*diagnosis/drug therapy/*secondary
MH  - Breast Neoplasms/*diagnosis/drug therapy
MH  - Clinical Trials as Topic/methods
MH  - Drug Administration Schedule
MH  - Female
MH  - Humans
MH  - *Standard of Care/standards
OTO - NOTNLM
OT  - biomarker
OT  - bisphosphonate
OT  - bone metastasis
OT  - breast cancer
OT  - de-escalated treatment
OT  - skeletal-related event
EDAT- 2015/07/01 06:00
MHDA- 2016/08/19 06:00
CRDT- 2015/07/01 06:00
PHST- 2015/05/06 00:00 [received]
PHST- 2015/06/24 00:00 [accepted]
PHST- 2015/07/01 06:00 [entrez]
PHST- 2015/07/01 06:00 [pubmed]
PHST- 2016/08/19 06:00 [medline]
AID - S0923-7534(19)36345-8 [pii]
AID - 10.1093/annonc/mdv284 [doi]
PST - ppublish
SO  - Ann Oncol. 2015 Nov;26(11):2205-13. doi: 10.1093/annonc/mdv284. Epub 2015 Jun 28.