Researchers led by Matthew Smith, MD, PhD, of the Massachusetts General Hospital, observed results from a phase 3 trial in order to reassess the efficacy of denosumab using symptomatic skeletal events (SSE) as the endpoint. Patients who had CRPC, were not previously exposed to bisphophonates and had radiographic evidence of bone metastasis were randomized to either denosumab 120 mg plus intravenous (IV) placebo every four weeks, or IV zoledronic acid 4 mg plus placebo every four weeks.
They found that patients with CRPC that were treated with denosumab were at a significantly reduced risk of developing first SSE, and first and subsequent SSEs, compared to those who were on zoledronic acid.
In patients who had no-to-mild pain at baseline, both SSEs and skeletal-related events (SREs) were associated with moderate-to-severe pain development. When defined as SSE versus SRE, fewer patients had skeletal complications – fractures in particular.
This study reassessed the efficacy of denosumab using symptomatic skeletal events (SSEs) as a prespecified exploratory end point. In patients with CRPC and bone metastases, denosumab reduced the risk of skeletal complications versus zoledronic acid regardless of whether the end point was defined as SSE or SRE.