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).


OBJECTIVE
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).


CONCLUSIONS
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.
Department of Internal Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, People's Republic of China; Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Zhiyu
Z
Wang
Department of Internal Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, People's Republic of China; Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Dan
D
Qiao
Department of Internal Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, People's Republic of China; Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Yaohong
Y
Lu
Department of Internal Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, People's Republic of China; Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Dana
D
Curtis
Department of Internal Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, People's Republic of China; Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Xiaoting
X
Wen
Department of Internal Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, People's Republic of China; Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Yang
Y
Yao
Department of Internal Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, People's Republic of China; Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA zhao-hui@sjtu.edu.cn.
Hui
H
Zhao
D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001847:Bone Diseases / Q000517:prevention & control* / Q000601:surgery; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary; D000069448:Denosumab / Q000627:therapeutic use; D004164:Diphosphonates / Q000627:therapeutic use; D006801:Humans; D000077557:Ibandronic Acid; D007093:Imidazoles / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy; D000077268:Pamidronate; D013117:Spinal Cord Compression / Q000517:prevention & control; D016896:Treatment Outcome; D000077211:Zoledronic Acid
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000069448:Denosumab; D000077211:Zoledronic Acid; D000077268:Pamidronate; D000077557:Ibandronic Acid
Bisphosphonates; Bone metastasis; Denosumab; Network meta-analysis; Skeletal-related events