Should de-escalation of bone-targeting agents be standard of care for patients with bone metastases from breast cancer? A systematic review and meta-analysis

Background: De-escalation of bone-targeted agents, such as bisphosphonates and denosumab, from 4-weekly to 12-weekly dosing is an increasingly used strategy in patients with bone metastases from breast cancer. It is unclear whether there is sufficient evidence to support de-escalation as a standard of care. Methods: A systematic review of randomised trials comparing standard 4-weekly administration of bone-targeted agents with de-escalated (q12-weekly) dosing in breast cancer patients was performed. Medline, PubMed and the Cochrane Register of Controlled Trials were searched from inception until November 2014 for relevant studies. Outcomes of interest included skeletal related event (SRE) rates, bone pain, adverse events and bone turnover biomarkers. Random effects meta-analyses were performed. Results: A total of 9 citations representing 7 unique studies were eligible. One study is ongoing with no reported data. Six studies reported data for at least one outcome of interest. Data was available comparing standard versus de-escalated therapy for pamidronate (1 study, 38 patients), zoledronate (3 studies, 1117 patients) and denosumab (2 studies, 284 patients). Meta-analysis of 5 trials reporting data for onstudy SRE rates between standard (61/443 patients) and de-escalated (49/392 patients) arms produced a summary risk ratio of 0.90 (95% CI 0.63-1.29). Meta-analyses of data for adverse events and bone turnover biomarkers also showed no statistically significant differences between standard and de-escalated arms, though only limited numbers of patients and events were present for most analyses. by gest on July 1, 2015 http://annofordjournals.org/ D ow nladed from