Phillip Koo:

So we're gonna move on now to metastatic castration-resistant prostate cancer, and we're gonna talk about the ARTO trial, which is long-term… well, I'll let you describe it, but this is an mCRPC.

Zachary Klaassen:

Yeah, so this is patients that have metastatic disease that have already become resistant to hormone therapy, and so this is low-volume mCRPC, so you can see the definition at the top, less than 3 lesions, no visceral lesions, which means nothing in the lymph nodes, or excuse me, nothing in the bone, or the lungs or the liver.

And then, no prior therapies for mCRPC. So this is sort of when they first get diagnosed. So low volume, less than 3 lesions. These patients were then randomized to Abiraterone, which is one of our common treatments for mCRPC. They continue their ADT. And then the treatment, or the experimental arm.

was adding SBRT, which is a very short course of high-dose radiation to all of these three sites that were identified on imaging. And so, this trial's been going on for a while. So we talked about previously the captain trial will be falling on for a long time. This trial's been going on for over 7, 8 years, I believe.

And what we're seeing now is we can start to see these longer-term outcomes. So, overall survival was improved with this combination of continuing ADT plus Abiraterone, plus SBRT, as well as cancer-specific survival on the right.

Again, improved with the combination of all of the Abiraterone and SPRT and ADT. And important to note, Phil, this is a Phase 2 trial, so a smaller trial. You know, I think it was about just over 100 patients, I believe, and so they probably will move this into a Phase 3 setting. We're already sort of seeing some of this done in the clinics, but it's nice to have some data that if these are amenable to SBRT, it's not unreasonable to treat them, and certainly, this is a very practice-informing trial with these longer follow-up results from the ARDO trial.

Phillip Koo:

You know, this is interesting, because I think a lot of the patients on the line are listening and watching have seen something similar, and we do this METS-directed therapy for oligometastatic disease in patients who have biochemical recurrence. So, after you get radiation or surgery, your PSA starts coming up, and then you start zapping some pelvic lymph nodes or whatnot.

But in those trials, oftentimes we're delaying ADT. We're putting it off, because you could control the disease with just the lasers and radiation. This is a little different, and I think it's real important to recognize that these patients, I believe, were receiving ADT plus Abiraterone plus, you know, that radiation treatment. So it's different, because I think, obviously, the disease is different. It's more aggressive in that castration-resistant state.

So, is this something that… you mentioned it is something that's sort of happening already. How should patients approach this when they might have, let's say, 3 METs and they're diagnosed as CRPC?

Zachary Klaassen:

Yeah, I think these are always important discussions, because it's… it… nothing's… Excuse me, nothing's ever free when you're getting the treatment, so you have to worry about side effects, you have to worry about… what's the ramifications of getting a treatment? The way that we're able to tailor this radiotherapy to these spots is actually pretty sophisticated these days, and so this can often help with symptoms, too. If people are having some bone pain from one of these spots.

It's often resolved quite quickly with radiation to those areas. So I… in our institution, we typically will discuss these at our multidisciplinary tumor board, where all the experts from all the different fields get together and discuss these cases. And I think, for the most part, this is… even though it's Phase 2 data, it's nice to have that, because we're already sort of seeing it. If you have a radiation oncologist that has SBRT, for them it's easy to give it. It's typically quite well tolerated, especially when it's given to the bone.

And so, we know there's going to be continued side effects with the Abiraterone, etc. But to see some benefit there, I think this is… this is already sort of snuck into the clinic in a good way, and now we have some data to perhaps support it.

Phillip Koo:

Great. So this is a question that comes often, and, you know, it makes a lot of sense, this question. Why are patients still put on ADT, even though it's failing and they're castration resistant?

Zachary Klaassen:

Yeah, it's a great question, one we get asked all the time. I typically… I typically discuss it as follows, is that… The majority of your cancer is still probably responding to that ADT. There's just a portion of it. It's always hard to depict whether it's 10% or 5%, but there's clearly a portion of it that has had mutations that is now resistant to it. So we're still treating the majority of it with the ADT, but we need extra to get the cells that have sort of escaped that mechanism.

Phillip Koo:

Great. And you know, it's interesting, because I think we're seeing a lot of trial, and we're going to talk about this with the last trial, but we're seeing the side effects of ADT, and I think there's a movement towards how do we get to treatments that don't incorporate ADT in the future, and I think that's going to be sort of the next horizon.