How does Xgeva (denosumab) help with prostate cancer?

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Last updated: May 21, 2025 • View editorial policy

From the Guidelines

Xgeva (denosumab) is a crucial treatment for preventing bone complications in prostate cancer patients with bone metastases, reducing the risk of skeletal-related events by 18% compared to zoledronic acid. This is based on a placebo-controlled double-blind study comparing denosumab to zoledronic acid for the prevention of skeletal morbidity in men with bone metastases from castration-resistant prostate cancer (CRPC) 1. The study found that denosumab extended the time to first skeletal-related event (SRE) from 17.1 to 20.7 months and reduced the cumulative mean number of SREs.

Key Benefits of Xgeva

  • Reduces the risk of skeletal-related events such as bone fractures, spinal cord compression, or the need for radiation or surgery to treat bone pain
  • Delays the time to first SRE and subsequent SREs
  • Improves quality of life for prostate cancer patients with bone metastases
  • Can be administered as a subcutaneous injection once every four weeks, with a standard dose of 120 mg

Important Considerations

  • Xgeva does not treat the cancer itself, but rather manages its bone complications
  • Patients should take calcium and vitamin D supplements while on Xgeva to prevent hypocalcemia (low blood calcium), a potential side effect
  • Other possible side effects include jaw problems (osteonecrosis), particularly in patients with poor dental health, so a dental examination before starting treatment is recommended
  • The use of Xgeva is recommended in all patients with CRPC and bone metastases, whether they are symptomatic or not, as it has been shown to reduce the overall risk of skeletal complications by 36% 1.

From the Research

Xgeva and Prostate Cancer

  • Xgeva, also known as denosumab, is a fully human monoclonal antibody that binds to the receptor activator of nuclear factor-κB ligand (RANKL) and inhibits RANKL-mediated bone resorption 2, 3.
  • In patients with prostate cancer, Xgeva has been shown to be effective in preventing skeletal-related events (SREs) such as pathological fractures, radiation therapy, surgery to bone, and spinal cord compression 3, 4.
  • Studies have demonstrated that Xgeva is superior to zoledronic acid in terms of delaying the time to first SRE in patients with castration-resistant prostate cancer 3.
  • Xgeva has also been shown to be effective in combination with other treatments, such as Samarium-153 (Sm-153) oxabifore, in reducing pain and improving bone scan results in patients with bone metastases from prostate cancer 5.

Mechanism of Action

  • Xgeva works by inhibiting the activity of RANKL, a protein that promotes bone resorption 2, 6.
  • By blocking RANKL, Xgeva reduces the formation of osteoclasts, which are the cells responsible for breaking down bone tissue 2, 6.
  • This leads to a decrease in bone resorption and an overall improvement in bone health 2, 6.

Clinical Implications

  • Xgeva is indicated for the prevention of SREs in patients with bone metastases from solid tumors, including prostate cancer 2, 4.
  • The use of Xgeva in patients with prostate cancer has been shown to improve outcomes and reduce the risk of SREs 3, 4.
  • Clinicians should consider the use of Xgeva in patients with prostate cancer who are at risk of SREs, particularly those with castration-resistant disease 6.

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.