Denosumab for treatment of bone metastases secondary to solid tumours: Systematic review and network meta-analysis

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. Crown Copyright (C) 2012 Published by Elsevier Ltd. All rights reserved.