Robert B. Den, MD
About 90% of patients with prostate cancer who develop metastases will develop growths in the bone, says Robert B. Den, MD. These bone metastases can severely impact a patient’s quality of life, so finding the right bone-targeting agents is imperative, he adds.
Commonly used bone-targeted agents for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) include zoledronic acid (Zometa), denosumab (Xgeva), and radium-223 dichloride (Xofigo).
During a presentation at the 2018 OncLive®
State of the Science Summit™ on Prostate Cancer, Den, an associate professor of radiation oncology at Thomas Jefferson University Hospital, discussed bone-targeting agents in prostate cancer. In an interview during the meeting, Den explained where the landscape currently stands with bone-targeting agents, and the potential future of combinations and novel strategies.
OncLive: Can you provide an overview on your lecture of bone-targeting agents in prostate cancer?
Prostate cancer is a unique malignancy in that it tends to have a preponderance of metastases to the bone. Bone metastases can impact a patient’s quality of life by causing severe bone pain, so this is an area where we have begun thinking about targeting the bone microenvironment specifically, in a sort of tumor agnostic way.
The focus of my talk was to look at 3 bone-targeting agents: zoledronic acid, denosumab, and radium-223. Most of the agents that target prostate cancer directly have been shown to improve survival, and also have benefit in terms of decreasing the rate of skeletal-related events. However, the 3 agents that I mentioned are designed to target the makeup of the bone.
Bone is generally made up of 2 components, calcium and phosphatase. Zoledronic acid works through the phosphatase side, radium-223 works through the calcium side, and denosumab works by decreasing a specific ligand called RANKL and decreases the osteoclastic activity of the bone.
The bone is on a constant “balance beam” that is both building and destroying bone all the time in every person. This balance is based on the production of bone by the osteoblasts and the reduction of bone by the osteoclasts, and denosumab decreases the osteoclastic activity. In contrast, radium-223 works as a calcium mimetic , so it works in place of calcium. It is incorporated naturally by the body into the bone, to cause uptake of the radium-223 specifically into the bone.
We know that this specifically targets the areas where there is increased bone formation, and prostate cancer tends to be a “blastic” disease, meaning that it is an area where the cancer cells cause the increase in bone formation. Thus, radium-223 gets targeted specifically to areas of increased prostate cancer. In the phase III randomized ALSYMPCA trial, we saw an overall survival (OS) benefit with the use of radium-223. This was quite remarkable because it was the first radiopharmaceutical to show an improvement in OS in men with prostate cancer.