Denosumab for treatment of bone metastases secondary to solid tumours

systematic review and network meta-analysis

John A Ford, Rob Jones, Andrew Elders, Clive Mulatero, Pamela Royle, Pawana Sharma, Fiona Stewart, Radha Todd, Graham Mowatt

Research output: Contribution to journalArticle

31 Citations (Scopus)
4 Downloads (Pure)

Abstract

Aim
To evaluate the evidence for denosumab for the treatment of bone metastases secondary to solid tumours and, using a network meta-analysis, indirectly compare denosumab with bisphosphonates and best supportive care.

Data sources
MEDLINE (1948 to April 2011), EMBASE (1980 to March 2011), Cochrane Library (all sections) (issue 1, 2011) and Web of Science with Conference Proceedings (1970 to May 2011) and additional meeting abstracts (2010 and 2011) were searched.

Study eligibility, participants and interventions
Only randomised controlled trials assessing denosumab, bisphosphonates or best supportive care in patients with bone metastases from any solid tumour were included.

Synthesis
Direct evidence comparing denosumab and zoledronic acid was assessed for breast cancer, prostate cancer and other solid tumours. Denosumab was compared with pamidronate and best supportive care through a network meta-analysis for each tumour type. The primary outcomes were time to first skeletal related event (SRE) and time to first and subsequent SRE. Secondary outcomes were skeletal morbidity rate, pain, quality of life (QoL) and overall survival.

Results
Denosumab was found to be more effective in delaying the time to first SRE and reducing the risk of first and subsequent SRE compared to zoledronic acid, placebo and pamidronate. In breast and prostate cancer, denosumab was effective in reducing skeletal morbidity rate compared with placebo. The lack of published data on pain and QoL meant that firm conclusions could not be made. Denosumab did not appear to have an affect on overall survival.

Limitations
Network meta-analyses are subject to uncertainties and potential biases.

Conclusions
Denosumab is effective in preventing SRE, but the effect on pain and QoL is unclear.
Original languageEnglish
Pages (from-to)416-430
Number of pages15
JournalEuropean Journal of Cancer
Volume49
Issue number2
Early online date18 Aug 2012
DOIs
Publication statusPublished - Jan 2013

Fingerprint

Neoplasm Metastasis
zoledronic acid
pamidronate
Bone and Bones
Neoplasms
Prostatic Neoplasms
Quality of Life
Diphosphonates
Pain
Therapeutics
Placebos
Breast Neoplasms
Morbidity
Network Meta-Analysis
Denosumab
Libraries
Uncertainty
Meta-Analysis
Patient Care
Randomized Controlled Trials

Keywords

  • denosumab
  • zoledronic acid
  • pamidronate
  • neoplasm metastasis
  • indirect estimation techniques

Cite this

Denosumab for treatment of bone metastases secondary to solid tumours : systematic review and network meta-analysis. / Ford, John A; Jones, Rob; Elders, Andrew; Mulatero, Clive; Royle, Pamela; Sharma, Pawana; Stewart, Fiona; Todd, Radha; Mowatt, Graham.

In: European Journal of Cancer, Vol. 49, No. 2, 01.2013, p. 416-430.

Research output: Contribution to journalArticle

Ford, JA, Jones, R, Elders, A, Mulatero, C, Royle, P, Sharma, P, Stewart, F, Todd, R & Mowatt, G 2013, 'Denosumab for treatment of bone metastases secondary to solid tumours: systematic review and network meta-analysis', European Journal of Cancer, vol. 49, no. 2, pp. 416-430. https://doi.org/10.1016/j.ejca.2012.07.016
Ford, John A ; Jones, Rob ; Elders, Andrew ; Mulatero, Clive ; Royle, Pamela ; Sharma, Pawana ; Stewart, Fiona ; Todd, Radha ; Mowatt, Graham. / Denosumab for treatment of bone metastases secondary to solid tumours : systematic review and network meta-analysis. In: European Journal of Cancer. 2013 ; Vol. 49, No. 2. pp. 416-430.
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abstract = "AimTo evaluate the evidence for denosumab for the treatment of bone metastases secondary to solid tumours and, using a network meta-analysis, indirectly compare denosumab with bisphosphonates and best supportive care.Data sourcesMEDLINE (1948 to April 2011), EMBASE (1980 to March 2011), Cochrane Library (all sections) (issue 1, 2011) and Web of Science with Conference Proceedings (1970 to May 2011) and additional meeting abstracts (2010 and 2011) were searched.Study eligibility, participants and interventionsOnly randomised controlled trials assessing denosumab, bisphosphonates or best supportive care in patients with bone metastases from any solid tumour were included.SynthesisDirect evidence comparing denosumab and zoledronic acid was assessed for breast cancer, prostate cancer and other solid tumours. Denosumab was compared with pamidronate and best supportive care through a network meta-analysis for each tumour type. The primary outcomes were time to first skeletal related event (SRE) and time to first and subsequent SRE. Secondary outcomes were skeletal morbidity rate, pain, quality of life (QoL) and overall survival.ResultsDenosumab was found to be more effective in delaying the time to first SRE and reducing the risk of first and subsequent SRE compared to zoledronic acid, placebo and pamidronate. In breast and prostate cancer, denosumab was effective in reducing skeletal morbidity rate compared with placebo. The lack of published data on pain and QoL meant that firm conclusions could not be made. Denosumab did not appear to have an affect on overall survival.LimitationsNetwork meta-analyses are subject to uncertainties and potential biases.ConclusionsDenosumab is effective in preventing SRE, but the effect on pain and QoL is unclear.",
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T2 - systematic review and network meta-analysis

AU - Ford, John A

AU - Jones, Rob

AU - Elders, Andrew

AU - Mulatero, Clive

AU - Royle, Pamela

AU - Sharma, Pawana

AU - Stewart, Fiona

AU - Todd, Radha

AU - Mowatt, Graham

N1 - Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

PY - 2013/1

Y1 - 2013/1

N2 - AimTo evaluate the evidence for denosumab for the treatment of bone metastases secondary to solid tumours and, using a network meta-analysis, indirectly compare denosumab with bisphosphonates and best supportive care.Data sourcesMEDLINE (1948 to April 2011), EMBASE (1980 to March 2011), Cochrane Library (all sections) (issue 1, 2011) and Web of Science with Conference Proceedings (1970 to May 2011) and additional meeting abstracts (2010 and 2011) were searched.Study eligibility, participants and interventionsOnly randomised controlled trials assessing denosumab, bisphosphonates or best supportive care in patients with bone metastases from any solid tumour were included.SynthesisDirect evidence comparing denosumab and zoledronic acid was assessed for breast cancer, prostate cancer and other solid tumours. Denosumab was compared with pamidronate and best supportive care through a network meta-analysis for each tumour type. The primary outcomes were time to first skeletal related event (SRE) and time to first and subsequent SRE. Secondary outcomes were skeletal morbidity rate, pain, quality of life (QoL) and overall survival.ResultsDenosumab was found to be more effective in delaying the time to first SRE and reducing the risk of first and subsequent SRE compared to zoledronic acid, placebo and pamidronate. In breast and prostate cancer, denosumab was effective in reducing skeletal morbidity rate compared with placebo. The lack of published data on pain and QoL meant that firm conclusions could not be made. Denosumab did not appear to have an affect on overall survival.LimitationsNetwork meta-analyses are subject to uncertainties and potential biases.ConclusionsDenosumab is effective in preventing SRE, but the effect on pain and QoL is unclear.

AB - AimTo evaluate the evidence for denosumab for the treatment of bone metastases secondary to solid tumours and, using a network meta-analysis, indirectly compare denosumab with bisphosphonates and best supportive care.Data sourcesMEDLINE (1948 to April 2011), EMBASE (1980 to March 2011), Cochrane Library (all sections) (issue 1, 2011) and Web of Science with Conference Proceedings (1970 to May 2011) and additional meeting abstracts (2010 and 2011) were searched.Study eligibility, participants and interventionsOnly randomised controlled trials assessing denosumab, bisphosphonates or best supportive care in patients with bone metastases from any solid tumour were included.SynthesisDirect evidence comparing denosumab and zoledronic acid was assessed for breast cancer, prostate cancer and other solid tumours. Denosumab was compared with pamidronate and best supportive care through a network meta-analysis for each tumour type. The primary outcomes were time to first skeletal related event (SRE) and time to first and subsequent SRE. Secondary outcomes were skeletal morbidity rate, pain, quality of life (QoL) and overall survival.ResultsDenosumab was found to be more effective in delaying the time to first SRE and reducing the risk of first and subsequent SRE compared to zoledronic acid, placebo and pamidronate. In breast and prostate cancer, denosumab was effective in reducing skeletal morbidity rate compared with placebo. The lack of published data on pain and QoL meant that firm conclusions could not be made. Denosumab did not appear to have an affect on overall survival.LimitationsNetwork meta-analyses are subject to uncertainties and potential biases.ConclusionsDenosumab is effective in preventing SRE, but the effect on pain and QoL is unclear.

KW - denosumab

KW - zoledronic acid

KW - pamidronate

KW - neoplasm metastasis

KW - indirect estimation techniques

U2 - 10.1016/j.ejca.2012.07.016

DO - 10.1016/j.ejca.2012.07.016

M3 - Article

VL - 49

SP - 416

EP - 430

JO - European Journal of Cancer

JF - European Journal of Cancer

SN - 0959-8049

IS - 2

ER -