De-escalation of bone-modifying agents in patients with bone metastases from breast cancer: a systematic review and meta-analysis
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Bone-modifying agents (BMAs) such as bisphosphonates and denosumab are usually administered every 4 weeks (standard) in patients with bone metastases from breast cancer to prevent skeletal-related events (SREs). Recent randomized controlled trials suggest every 12-week (de-escalated) dosing interval may be non-inferior. The objective of this systematic review and meta-analysis was to compare the efficacy and harms of standard with de-escalated administration of BMA’s in patients with bone metastases from breast cancer.
We searched Medline, PubMed, and the Cochrane Register of Controlled Trials from 1947 to March 14, 2018 and conference abstracts from (2014–March 14, 2018) for randomized clinical trials comparing every 4-week and every 12-week dosing interval of bone-modifying agents. Using PRISMA guidelines, meta-analyses were performed using random-effects models, with findings reported as risk ratios with 95% confidence intervals (CI).
From a total of 1311 citations, we identified 8 full-text articles and 1 abstract comprising data from 5 completed randomized clinical trials (n = 1807). Zoledronate administration every 12 weeks compared to every 4 weeks produced a summary risk ratio of 1.05 (95% CI 0.88–1.25) for patients with ≥ 1 on-study SRE indicating similar efficacy. These results did not differ whether patients had received prior intravenous bisphosphonate. De-escalation was associated with a non-statistically significant lower risk of increased creatinine (summary risk ratio 0.41 [95% CI 0.15–1.16]). Currently, there are insufficient data for pamidronate and denosumab de-escalation.
These data are supportive of de-escalation of zoledronate from onset for patients with bone metastases from breast cancer.
KeywordsBisphosphonates Denosumab Breast cancer Bone metastasis Skeletal-related event De-escalated treatment
This project received no outside funding and was supported with internal research funds.
Compliance with ethical standards
Conflict of interest
Dr. Awan reports participating in the Novartis Canada Advisory Board on the use of Ribociclib. Dr. Hutton reports personal fees from Cornerstone Research, outside the submitted work. Dr. van Poznak reports personal fees from UpToDate and institutional research funds from Bayer, outside the submitted work. The remaining authors declare that they have no conflicts of interest (Hilton, Mazzarello, Vandermeer, Bota, Stober, Sienkiewicz, Fergusson, Shorr, and Clemons).
This article does not contain any studies with human participants performed by any of the authors.
Not applicable as this is a systematic review.
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