Data on the use of denosumab (Xgeva) to improve bone metastases-free survival in men with high-risk prostate cancer was presented at the American Urological Association conference today for the first time. If approved by the Food and Drug Administration (FDA), the use of denosumab injections will be the first successful treatment for bone metastasis prevention in prostate cancer.
Results from a new Phase III clinical trial were presented by lead researcher, professor Matthew Smith, MD, PhD, director of the Genitourinary Malignancies Program at Massachusetts General Hospital Cancer Center. Patient data was collected from more than 1,400 men in 30 countries who were at high-risk for developing bone metastases (due to rising PSA levels despite hormone therapy). Compared to the controlled placebo, monthly denosumab treatment significantly increased bone metastasis-free survival. Denosumab treatment also increased the time it takes to first bone metastasis and the time it takes to develop asymptomatic bone metastases. These findings are "first in field" results.
No other systemic therapy has been shown effective in delaying the development of bone metastasis in men with aggressive, castrate-resistant prostate cancer. Prevention of bone metastasis represents an important unmet medical need in patients with advanced disease.
"Denosumab provides a new therapeutic strategy that is complimentary to other forms of treatment for men with prostate cancer," said Dr. Smith. "This widens the perception of metastasis prevention research as a much more attractive area for research and may be perceived as a very effective path for new drug development."
Dr. Smith has been a Prostate Cancer Foundation (PCF) funding recipient since 1997 for his work in improving prostate cancer survivorship. PCF has invested more than $1.8 million in Dr. Smith and his team's critical research projects on denosumab and treatment sciences on improving survivorship. The more than $1.8 million in funding support for Smith and denosumab from the Prostate Cancer Foundation came from peer-reviewed, non-corporate academic grants starting in 1997. Denosumab is manufactured by Amgen pharmaceuticals.
This is the first time researchers have been able to control the tumor micro-environment to prevent metastases. Denosumab prevents cancerous cells from recruiting normal cells to assist in adhering to bone and forming metastatic tumors. The treatment does this through the inhibition of RANKL, a protein that activates signals that lead to the breakdown of bones.
Denosumab is currently approved by the FDA for several other indications under generic names. Prolia was approved by the FDA on June 1, 2010 for the treatment of postmenopausal women with osteoporosis who are considered to be at high-risk for fractures. In November 2010, the FDA approved Xgeva to help prevent skeletal-related events (SREs) in hormone treated prostate cancer patients whose cancer had metastasized to bone.
"Denosumab targets the microenvironment and has the potential to achieve what many other treatments have not," said Jonathan W. Simons, MD, president and CEO of PCF. "A compound that was once intended to prevent or slow bone metastases which improves survival is a new and unprecedented concept. It is an important first-in-class discovery in prostate cancer care."
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