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Pivotal Role Remains With Bone-Targeting Agents in mCRPC

Gina Columbus @ginacolumbusonc
Published: Tuesday, Sep 26, 2017

Dr. Charles J. Ryan from the University of California San Francisco
Charles J. Ryan, MD
Prostate cancer researchers are continuing to explore strategies to optimally integrate bone-targeted agents into patient care.

For example, an ongoing trial is assessing the combination of a radiopharmaceutical, radium-223 dichloride (Xofigo), with an androgen receptor-directed therapy, either abiraterone acetate (Zytiga) or enzalutamide (Xtandi). The open-label, phase IIa study is accruing patients with metastatic castration-resistant prostate cancer (mCRPC). The primary endpoint of the trial, which hopes to enroll 68 patients, is patient bone scan response rate (NCT02034552).

Another trial expected to launch within the next year is investigating the combination of abiraterone plus radium-223 in patients with hormone-sensitive metastatic prostate cancer.

“That’s really the goal for practicing physicians as we talk through prostate cancer today, which is that we have this long menu of various therapies but we are trying to find the right treatment for the right patient at the right time,” explained Charles Ryan, MD.

Ryan, professor of medicine and urology, Thomas Perkins Distinguished Professor in Cancer Research, Helen Diller Family Comprehensive Cancer Center, and chair of the 2017 OncLive® State of the Science SummitTM on Genitourinary Cancers, lectured on the impact of bone-targeting agents in patients with mCRPC. In an interview during the event, he shed light on the evolution of zoledronic acid and denosumab (Xgeva), and the future role of radium-223 as it begins to be studied in combination regimens.

OncLive: How are bone-targeting agents used in the management of advanced prostate cancer?

Ryan: Bone-targeting agents are critically important, and that’s because 90% of men who die from prostate cancer die with boney metastases, and often they die because of the complications of boney metastases. While we continue our research and clinical development of new therapies that target the tumor directly, it’s also critically important to think about the bones and how we can protect them from tumor invasion, and, in fact, reduce the likelihood of the disease killing patients.

Therefore, I think of bone-targeting agents in 2 arenas. One are the bisphosphonates and the RANK-ligand targeted therapies. These have been in clinical use in prostate cancer for many years. They have a definitive role in conjunction with antitumor therapy; they prevent skeletal-related events or complications in the bone from tumor invasion. The 2 most widely utilized ones are zoledronic acid and denosumab. I highlighted those a little bit in terms of where they are in our clinical use. There are some questions still on when to optimally use them, when to not use them, how long to use them, and what to do about preventing the complications, the most serious of which is osteonecrosis of the jaw. 

Then, I transitioned to the development of radioisotopes, in particular radium-223. I spoke about samarium, which is more of historical interest than anything else. Samarium was developed as a palliative treatment for people with boney metastases. It did demonstrate reductions in opiate use and improvements in pain control, but it never demonstrated a survival benefit. Therefore, the development of radium-223 over the last few years has represented a major step forward in that it is a bone-targeted agent that also has antitumor properties and a survival benefit.

It is approved in multiple countries; it has widespread use in prostate cancer. I reviewed the science of the use of radium-223, the studies moving forward in which it will be combined with abiraterone in various contexts, and I talked about the potential complications of it, when to use it, as I emphasized the [the need to find the] right therapy for the right patient at the right time.

In your experience, when do you typically administer these agents and for how long?

With regard to the bisphosphates or RANK-ligand targeted therapies, I typically initiate them, hopefully, before the patient is at significant risk for boney complications—but is at risk for a boney complication. In other words, I don’t give it to prevent bone metastases; I give it only in patients who have bone metastases. I like to give it before I see things like pain developing or alkaline phosphatase rising, because I know those are adverse prognostic factors. In many ways, what we are trying to do is prevent complications. 


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Community Practice Connections™: 1st Annual International Congress of Oncology Pathology™: Towards Harmonization of Pathology and Oncology StandardsAug 30, 20182.0
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