Management of Advanced Prostate Cancer in Urology: Update on Androgen Receptor Inhibitors - Episode 10

Role of PSA Kinetics in nmCRPC Management

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Ashley E. Ross, MD, PhD, comments on the clinical significance of PSA response in patients with nmCRPC.

Neal Shore, MD, FACS: Ash, let me ask you, now that all 3 of these drugs, apa [apalutamide; Erleada], enza [enzalutamide; Xtandi], daro [darolutamide; Nubeqa] are available can you talk about the PSA [prostate-specific antigen] kinetics of what we saw in these trials and how that influences using these drugs. Many of our patients and families are incredibly wedded to the PSA. And then we will want to get into your earlier raised question about the role of PSMA [prostate-specific membrane antigen] PET [positron emission tomography] in this population.

Ashley E. Ross, MD, PhD: The PSA certainly declined dramatically compared to placebo in these agents, which is obvious and it was expected. That’s why it was nice to see the overall survival benefit drive home. For the patients, seeing their PSA decline is a meaningful thing for them. And then the morale they have is meaningful, particularly when you’re telling them that, “Hey, at the same time, we’re going to do this combination therapy. You’re going to live for a while. And you must have a high brow. You want to see your PSA decline. Take that positive attitude into preserving your bone health and your cardiovascular [CV] health by doing exercise, doing strength-bearing measures, by us taking a look at how we’re using—if applicable, thinking about your bone protective agents, etc.” They can optimize that longevity and prevent some of the potential toxicities, like falls and fractures. The interesting thing is that all of the agents, to me, could there be nuances in the mets [metastasis]-free survival? Could there be nuances? It’s hard to compare agents to each other. There’s biases in all the trials and the populations, and it’s impossible, unless there’s an actual head-to-head to compare agents to each other. This wasn’t in this setting, but as we’re talking about quality of life and tolerability, the ODENZA trial was just a phase 2, but recently reported in meetings, [and] was looking at people taking enza [enzalutamide] then daro [darolutamide], or daro [darolutamide] then enza [enzalutamide] in the CRPC [castration-resistant prostate cancer] setting, metastatic, and what would be their preference. And this was on the idea that all these drugs, apa [apalutamide], daro [darolutamide], and enza, [enzalutamide] may have different properties in terms of how they cross the blood-brain barrier and how they affect fatigue and cognition, etc. I’d like to hear the other panelists’ thoughts on that. But the results were, I thought, “Well, maybe daro [darolutamide] was going to be great,” but it wasn’t as strikingly. The ODENZA favored daro [darolutamide] a little bit. The results weren’t striking, and it’s hard to know, for me, which agent do I reach for, when? It’s a very difficult thing for me to figure out. And for me, as a urologist, the most important thing as we intensify therapy is do I maximize cardiovascular health, bone health, metabolic health, as I intensify these agents? And I can’t tell which to do. And to me, what the ODENZA trial told me is if someone’s having a tolerability issue on 1 drug, it’s not inappropriate to switch to a similar agent which may or may not be more tolerable by them. Usually, we switch due to disease progression, but here we’re switching due to toxicity. Those are my thoughts there. It’s a complicated, nuanced thing. And I know we’ll get to the PET issue soon.

Neal Shore, MD, FACS: No, these are great issues.

Transcript Edited for Clarity