Safety, Survival Advantages of Radium-223 Continue to Offer Benefit in mCRPC

Richard G. Stock, MD

The manageable safety profile of radium-223 dichloride (Xofigo) compared with other radiopharmaceuticals is appealing to oncologists treating castration-resistant prostate cancer (CRPC) that is metastatic to the bone, says Richard G. Stock, MD.

“With previous radiopharmaceuticals, there has been a limitation with bone marrow toxicity,” said Stock, senior faculty, Radiation Oncology, Mount Sinai Hospital. “Radium-223 really spares the bone marrow to a much greater degree than prior treatments, and that is why it has been embraced and much more widely utilized than any of the other radiopharmaceuticals.”

The FDA approved radium-223 in May 2013 based on findings from the phase III ALSYMPCA trial. In the study, radium-223 demonstrated a median overall survival of 14.9 months compared with 11.3 months with placebo for patients with bone-metastatic CRPC (HR, 0.70; P <.001).

It was also associated with a significant delay in both the median time to first symptomatic skeletal-related events and the time to an increase in PSA level.

OncLive: What is the optimal use of radium-223?

What is the mechanism of action for radium-223 and how does that compare with other agents in this space?

Today, the radiopharmaceutical is being investigated in earlier settings, in combinations, and at different doses. In interview with OncLive, Stock discusses the ideal patient for radium-223, its proper sequencing with mCRPC, and the future outlook for the therapy.Stock: Obviously, it has been shown to improve survival in patients who have both CRPC and progressive disease on hormonal therapy with multiple bone metastases. The optimal use is in a patient with metastatic disease that primarily has bone metastases and, most often, radium-223 has been used later on after other first-line therapies. I see an opportunity for it to be used earlier during the course of mCRPC.Radium-223 is radioactive and it has taken up sites of new bone formation. Where prostate cancer has metastasized to the bone is where you have very active bone formation, with bone being laid down by the body. It preferentially absorbs radium-223 and attacks the bone metastasis.

Where do you see radium-223 falling in terms of sequencing in mCRPC?

Do you think radium-223 will ever be used in an earlier setting?

How has the field of radiopharmaceuticals evolved over the years?

What else is on the horizon for radium-223?

This is opposed to external-beam radiation, where you are basically delivering a photon and depositing energy into the site of the disease. Radium-223 is actually picking up the radioactive material, which is similar to other bone-forming elements, and going directly to the area of bone metastasis.My experience has typically been to use radium-223 in patients who have failed other treatments, including the new androgen-targeted therapies, traditional hormonal therapies, and chemotherapy. Patients I tend to see in my practice have already received and failed on some of those treatments; they are receiving radium-223 because it is kind of the next in line in terms of treatment.There are some trials looking at moving it up that will hopefully come out and show that it has an improved efficacy earlier on in some patients.Many of the radiopharmaceuticals that have been previously used have targeted bone metastasis and they were actually very good at reducing it. The problem has been that they are very suppressive on the bone marrow. Radium-223 did not have these issues.It has become a mainline treatment, along with a bunch of other treatments in mCRPC. It has kind of fallen in line along with immunotherapy and androgen receptor—targeted therapy, and it has just opened up a whole new field for treating patients with mCRPC.