Case 3: Factors to Consider in mCRPC Treatment

EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Alicia Morgans, MD:What are you thinking about when you’re facing these patients in your urology clinic, Ken?

Kenneth Kernen, MD:I think bone health is critical for all of these men. Again, I think for a while it was overlooked, regarding what we’re doing to these patients. We put them on ADT [androgen deprivation therapy]. We give them all of these treatments. We don’t really do much for their bone health. We actually have our own bone clinic. If the patient is on ADT—and a patient like this would get an automatic referral—we make sure they’re getting calcium and vitamin D at optimal levels. And then, either zoledronic acid or denosumab. Again, I think that’s critical for his bone health.

And then after that it’s also important to talk about, how do you treat that metastatic lesion? In this setting where he’s castrate-resistant, we’re very much prone to radium-223. We believe in it. The ALSYMPCA trial was very good in these patients, so we’re trying to put as many patients on it as we can just because it’s another tool in the toolbox to help treat these men earlier. And again, I think if you look at data about treating men with low-volume bone metastasis—that was from, I think, 2014, in theBritish Journal of Cancer—they do better than when they have high-volume bone metastasis.

Again, I think everything we’re doing is trying to move earlier and earlier in treating these patients. Treating the lowest volume of disease that you can, I think, is better. We’re moving toward doing that as soon as possible.

Alicia Morgans, MD:Great. And from your perspective, Neal, what are you thinking as the urologist?

Neal Shore, MD, FACS:Well, the case is kind of interesting in that the testosterone level was in the high castrate range. The EAU [European Association of Urology] guidelines have come out rather boldly and said it should be less than 20 [ng/dL]. The AUA [American Urological Association], we haven’t done that. I’m a believer that if you’re going to institute ADT, lower is better. So I like the idea of getting below 20 [ng/dL], and hovering around that 45 [ng/dL] range is just barely castrate; that concerns me about this case. I’m curious, after he received his abiraterone, how was his testosterone level? I don’t know if you have that information, but of course, you’d like to see that really go down significantly because there’s still circulating androgen that’s stimulating the AR [androgen receptor]. Is it coming from the tumor? Is it coming from the adrenals? And theoretically, with the abiraterone, it’s covering that.

To Ken’s point, I completely agree that this is a good opportunity to be thinking about a really active drug that has survival prolongation in the bone metastatic CRPC [castration-resistant prostate cancer] group. With radium-223, there’s no doubt. What we see so often is what our colleagues in the United States and other parts of the world do: They do the switch. They do abiraterone to enzalutamide, or enzalutamide to abiraterone. There’s probably a little bit better data that you’ll get some efficacy going from abiraterone to enzalutamide; and a really small percentage with enzalutamide to abiraterone.

Kim Chi, MD, has done beautiful work on that. We know of the PLATO trial. And there are multiple retrospective and prospective trials that have really shown that it’s quite a short-lived benefit, if at all. So you said it. Why not go with a mechanism of action drug like radium-223? Then the question becomes, and we can talk about this: Would you add in enzalutamide while you’re giving the radium-223? Let’s talk about some of the notions around concomitant therapy of an AR in radium versus sequencing and layering it, and the effects on the bone compartment. And then also this is an interesting case, too, for the notion around genomic profiling, which I’m sure we’ll want to talk about.

Transcript edited for clarity.