Phillip Koo:

Hi, this is Phillip Koo and welcome to Prostate Cancer Patient Voices. Today, we're going to be covering a few trials that were presented at a large international meeting called ESMO. And we're going to focus on a few important trials that might impact prostate cancer care in the near future. And to walk us through those trials, we have Dr. Zach Klaassen, who's associate professor at Wellstar MCG Health. Zach, thank you again for joining us.

Zach Klaassen:

Yeah, of course, Phil. I'm happy to discuss some exciting trials kind of focusing on the metastatic hormone-sensitive prostate cancer space.

Phillip Koo:

You know, it's interesting, that metastatic hormone-sensitive space is a hot topic. It's great to see more trials and more resources being invested in to figure out how best to treat these patients sooner, perhaps harder, again, to improve clinical outcomes. And that really is the goal of all these trials, is to improve clinical outcomes while minimizing those adverse events, which it's vitally important that we talk about that.

Phillip Koo:

So we have a bunch of trials that you're going to highlight, and let's start with the first one called ARANOTE.

Zach Klaassen:

Yeah, thanks, Phil. So ARANOTE actually is a really exciting trial. So this was FDA-approved for darolutamide plus ADT in metastatic hormone-sensitive prostate cancer in June of 2025. And so oftentimes, this was presented at ESMO 2024, now we're at ESMO 2025, we start to see some of these subgroup analyses presented, which is always exciting just to see, asking the question, is it better tolerated in younger men, older men? How are these outcomes different, if at all?

And I think this is an important one because we start to see men in their 80s and even 90s that have recurrent prostate cancer picked up on imaging and seeing if this treatment not only works, but also is safe in these different populations. So this one specifically looked at the subgroup analysis by age. I'll quickly run through the ARANOTE trial design. So this is men with metastatic hormone-sensitive prostate cancer, ECOG performance at a two to, two to one randomization, two to darolutamide plus ADT, one to placebo plus ADT. The key primary endpoint was radiographic progression-free survival, and you can see a whole host of other key secondary endpoints.

And so on the bottom of the screen, I've pulled out two kind of key endpoints, obviously the primary endpoint of rPFS and time to mCRPC, which I always think is a clinically meaningful endpoint. And what we see here is that darolutamide plus ADT favored ADT alone in the overall population, which we already knew, but also in all of these age breakdowns, less than 65 years of age, 65 to 74, as well as greater than or equal to 75 years. And we see a very similar trend in time to mCRPC favoring the darolutamide arm.

So we know that it works in all of these age populations. So the question is, "Great, it works. Is it the same tolerability across these ages?" And if we look at the grade 3 to 4 adverse events amongst the different age groups at the top, we'll focus on the darolutamide group, we see 32.5% grade 3 to 4 adverse events in less than 65 years of age, 28 in ages 65 to 74, and 33.3 in greater than 75 years of age. So essentially very similar rates of adverse events. So that tells me that whether I have somebody who's in their 50s, or a candidate for ADT plus darolutamide, or somebody in their 80s or 90s, I know that it works in both of these age groups and I also know that it's about the same tolerability in both these age group, which really helps us have these discussions with our patients.

Phillip Koo:

So this is interesting, I think, for the listeners out there. You often have these large trials that report out, there's a lot of press, and then what happens is over time, there's more data accumulated, more data that could be analyzed, and then you could take a deeper dive into data and learn even more about certain select populations, and it's great to see that regardless of your age, you're seeing pretty much the same benefits and adverse events are not worse in one age group than another, which kind of makes sense with darolutamide and some of those CNS toxic effects that we don't see as often with that drug. Is that a safe comment?

Zach Klaassen:

I think that's safe. And I think even on a weekly basis, I'll see 82 or 83-year-old gentlemen, good performance status, and even before I saw this data, I knew that I could treat this patient with ADT and darolutamide, know that I'd get a good benefit, and hope that they tolerated it okay, and I think now this data tells me that they're going to tolerate that just as good as anybody who's younger than that or even older than that. So I think it gives us a little more information to share with the patients when we're having this treatment discussion.