Denosumab in patients with cancer and skeletal metastases: a systematic review
and meta-analysis.
Author(s): Peddi P, Lopez-Olivo MA, Pratt GF, Suarez-Almazor ME.
Affiliation(s): Division of General Internal Medicine, The University of Texas, MD Anderson
Cancer Center, Houston, TX 77030, USA.
Publication date & source: 2013, Cancer Treat Rev. , 39(1):97-104
BACKGROUND: We conducted a systematic review of the literature to determine the
efficacy and safety of denosumab in reducing skeletal-related events (SRE) in
patients with bone metastases.
METHODS: A literature search using MEDLINE, EMBASE, Web of Science and The
Cochrane Collaboration Library identified relevant controlled clinical trials
up-to-March 14, 2012. Two independent reviewers assessed studies for inclusion,
according to predetermined criteria, and extracted relevant data. The primary
outcomes of interest were SRE, time to first on-study SRE, and overall survival.
Secondary outcomes included pain, quality of life, bone turnover markers (BTM),
and adverse events.
RESULTS: Six controlled trials including 6142 patients were analyzed. Compared to
zoledronic acid, denosumab had lower incidence of SRE with a risk ratio (RR) of
0.84 (95% confidence intervals (CI) 0.80-0.88), delayed the onset of first
on-study SRE (RR 0.83; 95% CI 0.75-0.90) and time to worsening of pain (RR 0.84;
95% CI 0.77-0.91). No difference was observed in overall survival with pooled
hazard ratio of 0.98 (95% CI 0.90-1.0). For total adverse events, denosumab was
similar to zoledronic acid (RR 0.97; 95% CI 0.89-1.0). No significant differences
were observed in the frequency of osteonecrosis of the jaw (RR 1.4; 95% CI
0.92-2.1). Patients on denosumab had a greater risk of developing hypocalcemia
(RR 1.9; 95% CI 1.6-2.3).
CONCLUSIONS: Denosumab was more effective than zoledronic acid in reducing the
incidence of SRE, and delayed the time to SRE. No differences were found between
denosumab and zoledronic acid in reducing overall mortality, or in the frequency
of overall adverse events.
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