Catherine Marshall: Thanks for having me.
Zachary Klaassen: So the first one was A-DREAM presented by Dr. Choudhury, and this was really interesting. It's looking at interruption of treatment and seeing if we can recover testosterone and really good responders in that metastatic castration sensitive disease space. So maybe just a quick overview of the trial, and what your high level thoughts are of the data.
Catherine Marshall: I really like that study, first of all.
Zachary Klaassen: So do I'm.
Catherine Marshall: It was a single-arm study, small numbers, about 75 patients who were enrolled. And it took patients who had undetectable PSAs after 18 to 24 months, and everybody stopped treatment. So a couple of things about the trial. One, patients obviously, had to be willing to stop treatment. It did tend to skew a little bit in the lower risk, although they did have some patients who would've met criteria for high volume disease at diagnosis per charted. But what was interesting, and their primary endpoint was recovered testosterone and then treatment-free at 18 months. And about 40% of patients had met that endpoint.
Zachary Klaassen: That's pretty good.
Catherine Marshall: That is really good. And so I think that this comes up all the time for us in clinic when patients have really great responses to therapy. The question is always, well, what happens now? Do I continue? Do stop? We did not have a lot of data for what would happen if patients stopped, how long they could stop. And now this definitely provides that. The convention was that for metastatic disease, patients do not stop treatment. I really think that what this trial adds, is that now we need to reconsider that concept and really think about how we can really implement intermittent ADT. Does it work? What's the overall survival? What does it look like in practice for patients? Really interesting study I thought. Very useful for patient counseling, and I think will really inform future trials that we do. And I really think that this question of, do patients need lifelong testosterone suppression should be readdressed.
Zachary Klaassen: Yeah. Well said. Well, clinical practice is real world, and we have our patients that we'll just stop because we have to. But do you think this phase two did a great signal? Do you think it changes practice tomorrow? Do we need more information?
Catherine Marshall: I don't think it changes practice. I mean, I definitely have patients, I'm sure we all do, who want to stop therapy. I think for those patients who really want to stop therapy, this at least gives us some information to give those patients about what the course would look like. What are the features that make it more or less likely that they will have a recurrence in a short period of time? But I don't think that it changes practice for me at least for my standard patients.
Zachary Klaassen: Yeah, makes sense. Second trial, really interesting. We've been waiting a while to see the ARACOG data. This was presented by Dr. Morgans, and this is basically darolutamide versus enzalutamide sort of advanced prostate cancer patients. Maybe just walk through that trial design and some of the high-level results.
Catherine Marshall: Yes. So that was an interesting study too, because we don't have a lot of head-to-head comparisons for these ARPIs. And that study, the primary endpoint was looking at cognitive function. So in practice and sort of theoretically we had this idea that enzalutamide might cause more cognitive dysfunction because it crosses the blood-brain barrier, and we were comparing that to darolutamide, which doesn't have that cross of the blood-brain barrier. And what they found was that on the cognitive testing that they did, patients did worse with enzalutamide compared to darolutamide. There were some key things I think missing that we don't know yet just based on the abstract data. One, was there was no efficacy data presented. The other thing that I think was really interesting from that study was that it looked at patients who switched therapy, and there were a number of patients who were eligible for switching who switched to darolutamide, but nobody who switched from darolutamide to enzalutamide.
Problem with that is that darolutamide was offered for free, which certainly could have complicated why people were picking and choosing some of the treatment options too. And the other thing too is that we definitely don't routinely do that, cognitive testing in everybody in our clinic to sort of advise patients on how those changes are happening. But I think for some patients, cognitive function and cognitive changes that might happen are a big concern. The other thing that was missing from that study was how long patients were on androgen deprivation therapy prior to joining the study, which certainly could have influenced the results. But there are some patients who, when I give the long list of side effects that can happen from these therapies, cognitive dysfunction is their primary concern. And again, I think that this provides useful data for those patient discussions.
Zachary Klaassen: Yeah. Well said. I think you're right. I mean, some patients want to avoid hot flashes. Some want to avoid brain fog or cognitive changes. I think this adds some information to our counseling, and I think there'll be more to come from this trial I think too.
Catherine Marshall: Yeah, absolutely.
Zachary Klaassen: Your title of your talk was Minimizing Toxicity and Maximizing Outcomes. I think we have such a plethora of options for prostate cancer. That's a kind of a broad statement, but what are your thoughts on that title?
Catherine Marshall: Yes. So I think that we are in a good place in some of our states. Obviously, we still have a lot of work to do. I mean, we're not curing prostate cancer yet, but when we have a lot of options, we need to think about like, okay, we know that all of these drugs are active. And then when we're talking to patients, think about like, well, what's the best option? And we need to get better at that as a field to be able to figure out what's the best option in terms of benefiting me and helping with the cancer, but then also helping men to live normal lives with really minimal toxicity.
Zachary Klaassen: Yeah. No, this has a great discussion. I've enjoyed both these trials, and you gave a great breakdown of it. Thank you for joining us on UroToday.
Catherine Marshall: Thanks so much for having me.