Initiating Radium-223 Therapy in mCRPC

Daniel J. George, MD:Radium-223 is probably one of the hardest medicines for us to pinpoint the exact right time to use in a patient. The population is diverse. Some patients have bone-only metastatic disease, some have a mix. Some are oligometastatic with only a few large thick lesions, and others might have small diffuse lesions. We have patients who have bone metastases that are 20 to 40 in number. We have many patients with bone metastases that are 2 to 5 in number. None of these scenarios represent a perfect case for using radium. They’re all justifiable, particularly if they’re associated with subtle symptoms. I think the key is the subtle symptoms.

When patients have moderate to severe symptoms associated with their bone-burdened disease, it’s clear that radium-223 is a good choice. By the time that happens, these patients are late into their lives. There have been some older studies that have shown that by the time patients develop moderate degrees of pain associated with prostate cancer, their median survivals are 6 to 10 months. If we’re starting radium-223 in that setting, it’s too late. It takes 5 months to get this treatment into these patients. It’s too late for that population to see a survival benefit. We really need to be thinking about using this therapy when patients have 1 to 2 years to live, or longer. To do that, we need to be thinking not about treating moderate degrees of pain but treating patients early on for minimal pain or other symptoms associated with the metastatic disease that puts them at-risk for these boney complications like pain, fractures, and what not.

That’s a really critical part to thinking about when’s the optimal time. And layering, being able to use this drug on top of drugs like enzalutamide, really allows us to begin to think about that in some of these earlier disease settings. That’s not the only use. I use a lot of radium-223 by itself, off of hormonal therapies, because it can be very effective on that bone environment. In many cases, the benefits associated with those hormonal therapies have already largely passed. To me, we can kind of use this agent either way. I’m not sure either way is optimal. It depends on that patient’s circumstances, their PSA [prostate specific antigen] progression, and their symptoms. But that’s the population I want to think about using radium-223 in, primarily while those symptoms are happening early in their evolution.

To me, the goal with radium-223 is 6 doses of treatment. Why is that? We saw the greatest survival benefit associated with patients who got 6 doses. In the ALSYMPCA study, where the survival benefit was seen, the majority of these patients were performance status 0-1. These are patients who are essentially normal functioning patients. We’re not talking about patients who have a performance status of 2, where it’s too late, for the most part.

Thinking about good performance status patients is critical so that we can treat patients for a total of 6 doses. That’s the benefit that is associated with this. It’s not any 1 dose that’s really benefiting patients, it’s the complete course. It’s similar to chemotherapy. If we’re going to give chemotherapy, we’re not going to do it for 2 or 3 doses and see a survival benefit. It’s got to go on for at least 6 doses. Could we go longer with radium-223? That’s an open question. Right now, that’s not how we’re using the drug. That’s not what our data speak to. It might in the future, but I know that 6 cycles is what I really want to shoot for with these patients. Many of them get to the end of that and are still doing well. I’m OK stopping there because I know that the survival benefit was associated with 6 cycles.

I don’t try to go beyond that with my patients, but I do try to get there. For patients, it’s really helpful for them to know that there’s a stopping point. We’re not going to do this indefinitely. We’re going to do this for 6 doses, 5 months. We’re going to reevaluate and go from there.

Transcript edited for clarity.

mCRPC Treated With Radium-223 Therapy

January 2015

H&P:

• A 71-year old gentleman presented with urinary incontinence
• Past medical history: HBP controlled with lisinopril
• On digital rectal examination prostate was enlarged
• Patient was asymptomatic

Imaging:

• Transrectal ultrasound and biopsy revealed adenocarcinoma of the prostate gland with a Gleason score 9 [4+5] with 9 of 12 cores positive
  • PSA, 10.2 ng/mL
• CT scan was negative for metastases
• He was started on a 3-month depot injection of leuprolide 22.5 mg and treated with 7800 cGy IMRT

April 2016

• Patient returned for 3-month injection; his PSA level increased to 47 ng/mL
  • CT/Bone scans were negative for metastases
• He was started on enzalutamide
  • PSA, 12 ng/mL

October 2016

• 6 months later the patient complained of severe fatigue and lower back pain
  • Imaging with CT and bone scan showed multiple metastases of the spine and pelvis
  • PSA levels increased to 76 ng/mL
  • ALP, 268 U/I
• Radium-223 therapy was initiated in addition to continuing enzalutamide
• After 3 infusions of radium-223
  • PSA declined to 31 ng/mL
  • ALP decreased to 80 U/l
  • CT scan showed no new bone metastases
  • Fatigue decreased, and patient’s physical activity increased