Abstract

Skeletal-related events (radiation to bone, pathologic fracture, surgery to bone and spinal cord compression) often occur in patients with bone metastases secondary to solid tumours. A recent approach to treatment is the subcutaneous RANK ligand (RANKL) inhibitor, denosumab. RANKL is like bisphosphonates a key mediator of osteoclast-mediated bone loss and destruction in patients with bone metastases. A recent integrated analysis of three phase 3 studies that evaluated its efficacy in patients with bone metastases secondary to solid tumours versus the intravenous bisphosphonate zoledronic acid found that it was superior to the active control. Denosumab significantly delayed the median time to first skeletal-related event (SRE) by 8.2 months compared with zoledronic acid (p<0.0001). It also reduced the risk of a first SRE by 17% (p<0.0001), and reduced the risk of first and subsequent SREs by 18% (p<0.001). Adverse events were generally similar between the two treatment arms, however, in contrast with zoledronic acid, denosumab did not require monitoring or dose modification/withholding based on renal status. Incidence of acute-phase reactions was also lower in the denosumab treatment arm. Hypocalcaemia was, however, more commonly associated with denosumab. Osteonecrosis of the jaw occurred at a similar rate with both treatment options (p=0.13). Disease progression and overall survival were also similar when the two treatments were compared. This review considers the evidence to support the use of currently available treatment options to prevent skeletal-related events and considers their practical application from the perspective of the hospital pharmacist.