Systematic Literature Review and Network Meta-Analysis Comparing Bone-Targeted Agents for the Prevention of Skeletal-Related Events in Cancer Patients With Bone Metastasis

BACKGROUND: Complications from skeletal-related events (SREs) constitute a challenge in the care of cancer patients with bone metastasis (BM). OBJECTIVES: This study evaluated the comparative effectiveness of pamidronate, ibandronate, zoledronate, and denosumab in reducing the morbidity of SREs in cancer patients with BM. METHODS: Medline (1948 to January 2014), Embase (1980 to January 2014), the Cochrane Library (2014 issue 1), and Web of Science with Conference Proceedings (1970 to January 2014) were searched. Only randomized controlled trials assessing denosumab, bisphosphonates, or placebo in cancer patients with BM were included. The primary outcomes were SREs and SREs by type. The network meta-analysis (NMA) was performed with a random-effects Bayesian model. RESULTS: The NMA included 14 trials with 10,192 patients. Denosumab was superior to placebo in reducing the risk of SREs (odds ratio OR: 0.49; 95% confidence interval CI: 0.31-0.75), followed by zoledronate (OR: 0.57; 95% CI: 0.41-0.77) and pamidronate (OR: 0.55; 95% CI: 0.41-0.72). Ibandronate compared with placebo could not reduce the risk of SREs. Denosumab was superior to placebo in reducing the risk of pathologic fractures (OR: 0.50; 95% CI: 0.32-0.79), followed by zoledronate (OR: 0.61; 95% CI: 0.43-0.86). Denosumab was superior to placebo in reducing the risk of radiation (OR: 0.51; 95% CI: 0.35-0.75), followed by pamidronate (OR: 0.67; 95% CI: 0.52-0.86) and zoledronate (OR: 0.70; 95% CI: 0.52-0.96). CONCLUSION: This NMA showed that denosumab, zoledronate, and pamidronate were generally effective in preventing SREs in cancer patients with BM. Denosumab and zoledronate were also associated with reductions in the risk of pathologic fractures and radiation compared with placebo. Denosumab was shown to be the most effective of the bone-targeted agents.