Adjuvant bisphosphonates or RANK-ligand inhibitors for patients with breast cancer and bone metastases: A systematic review and network meta-analysis

Y Tesfamariam; T Jakob; A Wöckel; A Adams; A Weigl; I Monsef; K Kuhr; N Skoetz

doi:10.1016/j.critrevonc.2019.02.004

Adjuvant bisphosphonates or RANK-ligand inhibitors for patients with breast cancer and bone metastases: A systematic review and network meta-analysis

Crit Rev Oncol Hematol. 2019 May:137:1-8. doi: 10.1016/j.critrevonc.2019.02.004. Epub 2019 Feb 19.

Authors

Y Tesfamariam¹, T Jakob¹, A Wöckel², A Adams³, A Weigl¹, I Monsef¹, K Kuhr³, N Skoetz⁴

Affiliations

¹ Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
² Department for Gynecology and Obstetrics, University Hospital Würzburg, Würzburg, Germany.
³ Institute of Medical Statistics and Computational Biology, University of Cologne, Cologne, Germany.
⁴ Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany. Electronic address: nicole.skoetz@uk-koeln.de.

PMID: 31014505
DOI: 10.1016/j.critrevonc.2019.02.004

Abstract

Bone-modifying agents like bisphosphonates and receptor activator of nuclear factor kappaβ ligand (RANK-L) inhibitors are used as supportive treatments in breast cancer patients with bone metastases to prevent skeletal-related events (SREs). Due to missing head-to-head comparisons, a network meta-analysis was performed to provide a hierarchy of these therapeutic options. Through a systematic literature search, 21 randomized controlled trials (RCTs) that fulfilled the inclusion criteria were identified. To prevent SREs, the ranking through P-scores showed denosumab (RR: 0.62; 95%CI: 0.50-0.76), zoledronic acid (RR: 0.72; 95%CI: 0.61-0.84) and pamidronate (RR: 0.76; 95%CI: 0.67-0.85) to be significantly superior to placebo. Due to insufficient or heterogeneous data, overall survival, quality of life, pain response and adverse events were not able to be analyzed within the network. Although data were sparse on adverse events, the risk of significant adverse events appeared low. The results of this review can therefore be used to formulate clinical studies more precisely in order to standardise and focus on patient-relevant outcomes.

Keywords: Bisphosphonates; RANK-L inhibitors; RCTs; SREs.

Publication types

Meta-Analysis
Systematic Review

MeSH terms

Adjuvants, Immunologic / administration & dosage
Bone Density Conservation Agents / administration & dosage*
Bone Neoplasms / drug therapy*
Bone Neoplasms / secondary*
Breast Neoplasms / drug therapy*
Breast Neoplasms / pathology
Diphosphonates / administration & dosage*
Female
Humans
Network Meta-Analysis
Quality of Life
Randomized Controlled Trials as Topic
Receptor Activator of Nuclear Factor-kappa B / antagonists & inhibitors*

Substances

Adjuvants, Immunologic
Bone Density Conservation Agents
Diphosphonates
Receptor Activator of Nuclear Factor-kappa B
TNFRSF11A protein, human