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Patient Selection for Radium-223 in mCRPC

Panelists: Judd Moul, MD, Duke Cancer Institute; Neeraj Agarwal, MD, Hunstman Cancer Institute; Tanya Dorff, MD, City of Hope National Medical Center; Alicia Morgans, MD, PhD, Northwestern University Feinberg School of Medicine
Published: Thursday, Sep 12, 2019



Transcript: 

Judd Moul, MD: Neeraj, can I ask you a practical question? In your clinical practice, when would you think about radium-223? Give me an example of a patient you would sequence that in.

Neeraj Agarwal, MD: As we get into the CRPC [castration-resistant prostate cancer] space now, when patients have already been treated with docetaxel in a hormone-sensitive setting, the whole arsenal is pretty small. You mentioned radium, and we have enzalutamide or abiraterone, but I don’t see many drugs beyond that, except for cabazitaxel or maybe Sipuleucel-T, which we don’t use frequently. When you have such a limited number of options, and PSA [prostate-specific antigen] is rising and bone metastasis is a dominant disease presentation, I always think about radium.

Judd Moul, MD: If that patient had been on abiraterone or enzalutamide, from a practical standpoint, should there be a drug holiday between when you stop the ABI [abiraterone] or the ENZA [enzalutamide] and begin the radium-223? Do you stop it and then send the patient to nuclear medicine or radiation oncology? Do you have to be off it for a couple of months?

Neeraj Agarwal, MD: No. It’s very clear in my mind that abiraterone cannot and should not be combined with radium. I do not think we have any data to tell us whether enzalutamide should become combined with radium. I think it’s safe to combine radium with enzalutamide. I see that our own trial is mentioned here. We did a small 50-patient randomized trial looking at safety bone markers, and it’s going beyond that, looking at the phase III data. I think both agents are very safe, as far as this combination is concerned. Enzalutamide is appropriate with radium as long as you’re using bone-strengthening agents.

I do not want anybody to stop receiving enzalutamide while they’re receiving radium, based on the fact that we don’t have any data to dispute it. It’s a very regular practice. In my view, if somebody’s PSA is going up rapidly, we know that radium is not a drug that really lowers PSA or decreases the size of the lymph nodes. It is a bone-targeting agent, so while you are targeting the bone, we can control disease elsewhere. That’s why I use enzalutamide.

I use enzalutamide concurrently with radium. There are no data for it, but radium was used with standard of care in the ALSYMPCA trial, and enzalutamide is the standard of care. As long as I don’t see any safety issues, I will continue to use radium with standard of care, which was the eligibility criteria for the ALSYMPCA trial. The labeling for radium allows you to treat patients with other standard-of-care therapy. From a safety perspective, I do not see any excessive fracture risk, as long as you’re using denosumab or bisphosphonates, which we should be using regardless.

Judd Moul, MD: Regarding the denosumab, the current standard is now 120 mg monthly if we’re going to use denosumab. Although Amgen has a trial—I don’t think it’s reported out completely—comparing 1 month with every 3 months to see if perhaps a 3-month dose decreases the incidence of osteonecrosis or other adverse effects. That would correspond nicely with the 3-month LHRH [luteinizing hormone-releasing hormone] agents. Right now, we don’t know if that’s how that trial is going to read out.


Transcript Edited for Clarity 

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Transcript: 

Judd Moul, MD: Neeraj, can I ask you a practical question? In your clinical practice, when would you think about radium-223? Give me an example of a patient you would sequence that in.

Neeraj Agarwal, MD: As we get into the CRPC [castration-resistant prostate cancer] space now, when patients have already been treated with docetaxel in a hormone-sensitive setting, the whole arsenal is pretty small. You mentioned radium, and we have enzalutamide or abiraterone, but I don’t see many drugs beyond that, except for cabazitaxel or maybe Sipuleucel-T, which we don’t use frequently. When you have such a limited number of options, and PSA [prostate-specific antigen] is rising and bone metastasis is a dominant disease presentation, I always think about radium.

Judd Moul, MD: If that patient had been on abiraterone or enzalutamide, from a practical standpoint, should there be a drug holiday between when you stop the ABI [abiraterone] or the ENZA [enzalutamide] and begin the radium-223? Do you stop it and then send the patient to nuclear medicine or radiation oncology? Do you have to be off it for a couple of months?

Neeraj Agarwal, MD: No. It’s very clear in my mind that abiraterone cannot and should not be combined with radium. I do not think we have any data to tell us whether enzalutamide should become combined with radium. I think it’s safe to combine radium with enzalutamide. I see that our own trial is mentioned here. We did a small 50-patient randomized trial looking at safety bone markers, and it’s going beyond that, looking at the phase III data. I think both agents are very safe, as far as this combination is concerned. Enzalutamide is appropriate with radium as long as you’re using bone-strengthening agents.

I do not want anybody to stop receiving enzalutamide while they’re receiving radium, based on the fact that we don’t have any data to dispute it. It’s a very regular practice. In my view, if somebody’s PSA is going up rapidly, we know that radium is not a drug that really lowers PSA or decreases the size of the lymph nodes. It is a bone-targeting agent, so while you are targeting the bone, we can control disease elsewhere. That’s why I use enzalutamide.

I use enzalutamide concurrently with radium. There are no data for it, but radium was used with standard of care in the ALSYMPCA trial, and enzalutamide is the standard of care. As long as I don’t see any safety issues, I will continue to use radium with standard of care, which was the eligibility criteria for the ALSYMPCA trial. The labeling for radium allows you to treat patients with other standard-of-care therapy. From a safety perspective, I do not see any excessive fracture risk, as long as you’re using denosumab or bisphosphonates, which we should be using regardless.

Judd Moul, MD: Regarding the denosumab, the current standard is now 120 mg monthly if we’re going to use denosumab. Although Amgen has a trial—I don’t think it’s reported out completely—comparing 1 month with every 3 months to see if perhaps a 3-month dose decreases the incidence of osteonecrosis or other adverse effects. That would correspond nicely with the 3-month LHRH [luteinizing hormone-releasing hormone] agents. Right now, we don’t know if that’s how that trial is going to read out.


Transcript Edited for Clarity 
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