De-escalation of Bone-Targeting Agents Appears Safe

A new meta-analysis suggests that de-escalation of bone-targeted agents such as bisphosphonates and denosumab is a safe strategy in patients with bone metastases from breast cancer. There is a growing body of evidence suggesting such de-escalation will soon be considered standard of care.

Bone-targeted agents are generally given every 3 to 4 weeks beginning at the time of diagnosis of bone metastases, until death. “If de-escalation of treatment is as efficacious as 3–4 weekly dosing, it could reduce clinic visits, drug side effects for patients, in addition to reducing costs to both the patient and the health care system,” wrote study authors led by Mark Clemons, MD, of the Ottawa Hospital Cancer Centre in Canada.

Clemons and colleagues conducted a systematic review and meta-analysis of published research on de-escalation of bone-targeted agents; six studies reported data for at least one “outcome of interest” involving pamidronate, zoledronate, and denosumab. Results of the analysis were published online ahead of print in Annals of Oncology.

The meta-analysis portion looked at five trials; in those, there were skeletal-related events (SREs) reported in 61 of 443 patients on standard dosing schedules, and in 49 of 392 de-escalated dosing patients, producing a non-significant summary risk ratio of 0.90 (95% CI, 0.63–1.29).

Other outcomes also appeared to be similar between groups. For example, two studies reported pain outcomes, and found no significant differences with regard to bone pain in standard and de-escalated dosing patients. There were also no significant differences in terms of bone turnover biomarkers such as C-telopeptides and N-telopeptides.

Adverse events (AEs) were difficult to compare across studies because of differing assessment methods. However, the researchers did analyze on-study renal AEs from five of the studies. There were 23 such events in the standard dose patients, and 20 events in the de-escalated dose patients, for a summary risk ratio of 0.86 (95% CI, 0.48–1.53).

The authors stressed that there are limitations inherent to this type of analysis, including differences in trial design and which outcomes were reported. “Despite these limitations, it is of interest to note that there were consistent patterns across all trials, irrespective of the bone-targeted agent under investigation,” they wrote. “There was no signal that de-escalation was associated with increased SRE risk or pain.”

The authors concluded that data from ongoing large trials will help clarify this issue, but the data increasingly support de-escalation as the standard of care.