Management of bone metastasis with intravenous bisphosphonates in breast cancer: a systematic review and meta-analysis of dosing frequency

Abstract

Bisphosphonates are wildly used in breast cancer patients with bone metastasis and generally administrated every 4weeks to lessen the risk of subsequent skeletal-related events. Bisphosphonates administration every 12weeks is also recommended in some guidelines. Recent clinical trials suggested that bisphosphonate treatment with reduced frequency (every 12weeks) to be non-inferior to standard therapy. The object of this analysis was to contrast the efficacy and safety of these two treatment strategies. We systematically retrieved databases such as MEDLINE, PubMed, Embase, and Cochrane library from 1947 to present for clinical trials comparing the efficacy between standard (every 4weeks) and de-escalation (every 12weeks) treatment of bisphosphates. We identified 4 articles with available data from 4 randomized clinical trials (n= 1721). Administration of bisphosphate every 12weeks was non-inferior to administration every 4weeks. There existed no significant difference in on-study skeletal-related events, renal dysfunction, and osteonecrosis of jaw. In the exploratory study, patients who received intravenous bisphosphates before enrollment experienced less on-study skeletal-related events and significant difference was observed between groups. This analysis suggested that de-escalation treatment with bisphosphates may be superior to standard treatment in terms of efficacy, safety, and economic costs. But it would be better that all the patients receive bisphosphates every 4weeks for several months before de-escalation.