Skeletal-related events (SREs) are complications of bone
metastases and carry a significant patient and economic burden.
Denosumab is a receptor activator of nuclear factor-κB
ligand (RANKL) inhibitor approved for SRE prevention in patients with
multiple myeloma and patients with bone
metastases from solid
tumors. In phase 3 trials,
denosumab showed superiority to the
bisphosphonate zoledronate in reducing the risk of first on-study SRE by 17% (median time to first on-study SRE delayed by 8.2 months) and the risk of first and subsequent on-study SREs by 18% across multiple solid
tumor types, including some patients with
multiple myeloma.
Denosumab also improved
pain outcomes and reduced the need for strong
opioids. Additionally, a phase 3 trial showed
denosumab was noninferior to
zoledronate in delaying time to first SRE in patients with newly diagnosed
multiple myeloma.
Denosumab has a convenient 120 mg every 4 weeks recommended dosing schedule with subcutaneous administration. Rare but serious toxicities associated with
denosumab include
osteonecrosis of the jaw,
hypocalcemia, and atypical
femoral fracture events, with multiple vertebral fractures reported following treatment discontinuation. After a decade of real-world clinical experience with
denosumab, we are still learning about the optimal use and dosing for
denosumab. Despite the emergence of novel and effective antitumor
therapies, there remains a strong rationale for the clinical utility of antiresorptive
therapy for SRE prevention. Ongoing studies aim to optimize clinical management of patients using
denosumab for SRE prevention while maintaining safety and efficacy.