Gomella Discusses Radium-223 Impact in mCRPC

Leonard G. Gomella, MD

Radium-223 dichloride (Xofigo) was originally developed as a palliative agent, similar to the earlier radiopharmaceuticals strontium-89 (Metastron) and samarium-153 (Quadramet), explains Leonard Gomella, MD.

“It was looked at as a palliative agent but, suddenly, people realized that there was a survival advantage,” says Gomella, physician, professor, and chair of the Department of Urology at Thomas Jefferson University and director of the Kimmel Cancer Center Network. “It has proven itself in several randomized trials, where it showed both an improved survival and quality of life.”

One such trial was the ALSYMPCA trial, where radium-223 demonstrated a median overall survival of 14 months versus 11.2 months with placebo (HR, 0.70; P = .00185) in patients with castration-resistant prostate cancer with bone metastases (mCRPC). In the trial, radium-223 also proved to have a manageable toxicity profile, adds Gomella.

OncLive: Who is the ideal patient to receive radium-223?

In an interview with OncLive, Gomella discusses the optimal patient population to receive radium-223 and how oncologists should best use it. He also discusses possible combination regimens and other advancements on the horizon regarding radium-223.Gomella: Radium-223, because of its unique mechanism of action and how good it is at targeting bone disease, is best for use in patients with mCRPC without visceral metastatic disease. If you focus in that area, it can really be used anywhere in the spectrum of patients with metastatic disease.

Are there any side effects with radium-223 that oncologists should be aware of?

Sometimes, there is a little bit of debate in the literature regarding whether patients really have that much pain relief with the agent if they have multiple painful boney metastases. In our experience, patients do get significant relief if they have boney metastasis, even though that is not what it is indicated for.There are some patients who experience neutrophilia or have reduced counts with radium-223. However, compared with other radiopharmaceuticals, it is much less common.

Oncologists should check the baseline complete blood count in patients to make sure that they are not suppressing their bone marrow. It doesn’t happen that often, but it needs to be monitored. There is also sometimes a little bit of gastrointestinal disturbance because of the excretion.

What potential does radium-223 have for use in combination?

It’s pretty mild. Most of the time, if you warn patients about some of these mild side effects, they are much more easily managed than if you don’t warn them.We have some experience. We have published some work out of our multidisciplinary clinic of combining radium-223 with some of the androgen receptor pathway blockers.

What are your thoughts on administering radium-223 in earlier lines of therapy?

Looking ahead, what do you see on the horizon for radium-223?

There are very small pilot studies investigating this, and our main objective has been to look at the toxicities. We haven’t see any additional toxicities with the combination. These are small studies. They are not really meant to show survival advantages or clinical outcomes; we are really only looking at the toxicity profile.It can be administered anywhere in the spectrum, and I think we are going to see more research in this area. In our multidisciplinary clinic—when we work with our radiation oncologists—it is not usually used upfront. We tend to use other agents upfront. It is not wrong to do it but, because of its mechanism of action and how it works with bone metastatic disease, we tend to use it a little bit later.We are going to see it studied earlier in the course of disease. We are going to see the results of some ongoing studies on retreatment with radium-223. That is certainly something that has a lot of interest.

The whole issue of sequencing is big in the mCRPC space right now, as well. Certainly, the sequencing of radium-223 with other agents will be occupying our time over the next several years to figure out the optimal approach.