Prevention of Symptomatic Skeletal Events with Denosumab Administered Every 4 Weeks Versus Every 12 Weeks–A Non-Inferiority Phase III Trial: Sakk 96/12 - Reduse

Practical Update for the Use of Bone-Targeted Agents in Patients with Bone Metastases from Metastatic Breast Cancer or Castration-Resistant Prostate Cancer

“…The rationale for the use of bisphosphonates in the treatment of patients with prostate cancer comes from studies showing that abnormal osteoblastic bone formation is associated with osteoclastic bone resorption and an elevation in osteoclastic markers 31,32 . Multiple randomized trials have shown significant reductions in the frequency of sres in patients with bone metastases from a variety of solid tumours that are treated with an osteoclast inhibitor; the use of such agents is therefore recommended for most patients with bone metastases from solid tumours, regardless of whether those metastases are osteolytic or osteoblastic 15,[33][34][35] .…”

“…A recent trial that evaluated the noninferiority of 12-weekly compared with 4-weekly dosing for btas suggested that the same dose-de-escalated schedule could also be applied to denosumab 44 . To direct future treatment recommendations, one ongoing clinical trial is currently comparing 12-weekly with 4-weekly denosumab in patients with mbca and crpc 33,45 . Data so far would suggest that de-escalation of all commonly used bone agents, including denosumab, to 12-weekly therapy is a reasonable clinical strategy.…”

“…As a result, the question of the duration of bta use should take into consideration life expectancy, overall burden of disease, and risk of sres in each individual patient. Most clinical trials have evaluated the use of btas for only a maximum of 2 years, and hence no high-quality evidence to support their use beyond 2 years has been developed [33][34][35] . Duration of use is currently being further evaluated in a series of Canadian studies.…”

De-Escalation of Bone-Targeted Agents for Metastatic Prostate Cancer

“…We were interested in randomized trials that had evaluated de-escalation of any established bone-targeted agent (for example, zoledronate and denosumab) against the standard 4-weekly treatment. Our systematic review was conducted as outlined in the Cochrane handbook, and only two studies met our inclusion criteria 4,5 .The study by Fizazi et al 4 was a phase ii open-label randomized trial in which 33 patients with mcrpc were randomized to either subcutaneous denosumab 180 mg every 4 weeks (n = 17) or every 12 weeks (n = 16). All patients randomized to denosumab had received treatment with zoledronic acid before randomization.…”

“…We were interested in randomized trials that had evaluated de-escalation of any established bone-targeted agent (for example, zoledronate and denosumab) against the standard 4-weekly treatment. Our systematic review was conducted as outlined in the Cochrane handbook, and only two studies met our inclusion criteria 4,5 .…”