Denosumab in patients with cancer and skeletal metastases: a systematic review and meta-analysis.
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.
Division of General Internal Medicine, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
Prashanth
P
Peddi
Maria A
MA
Lopez-Olivo
Gregory F
GF
Pratt
Maria E
ME
Suarez-Almazor
D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D000069448:Denosumab; D004164:Diphosphonates / Q000627:therapeutic use; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D016032:Randomized Controlled Trials as Topic; D000077211:Zoledronic Acid
D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000069448:Denosumab; D000077211:Zoledronic Acid