Treatment Considerations After New Data: ARASENS, ARANOTE, and PEACE-3

In part three of this prostate cancer roundtable discussion, the panel examines the latest clinical trials shaping prostate cancer treatment, including ARASENS, ARANOTE, and PEACE-3. This expert panel, moderated by Dr. David Morris, evaluates how these studies may influence the use of doublet and triplet therapies in metastatic hormone-sensitive and castration-resistant prostate cancer. From assessing the safety and efficacy of darolutamide to understanding its role across high- and low-volume disease, the conversation highlights the practical applications of these findings for oncologists in both academic and community settings.

Watch the fourth part of this series: The Growing Field of Radioligand Therapy and Radium Use for mHSPC and mCRPC

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Dr. Morris:
So, it’s already come up tonight once already the ARASENS trial as one of the triplet trials most recently published, you mentioned the high-volume/low-volume being similar in terms of outcomes. Has that increased your utilization of you think triplet therapy versus what it was before, and has it changed your preferred AR partner for those patients who are going into a triplet? You think a triplet is best?

Dr. Tan:
Yeah, I’ve always been a fan of the darolutamide being probably the ARSi with the least amount of drug-drug interactions, not significant amount of cardiovascular toxicity, hypertension, etc. And some of the other ARSi’s can have neurologic side effects, rash. So darolutamide is very similar in structure but slightly different enough. So it has a cleaner side effect profile.

So yes, according to that data, high-volume/low-volume did very similarly. And I think if you have a robust enough patient, even with low volume disease, we’re trying to get them the longest overall survival and radiographic progression-free survival. I think that is being used a lot more in all comers I would say.

Dr. Morris:
Okay. Similar with the side effect is a choice for an AR backbone good experience so far with darolutamide after the ARASENS trial was released?

Dr. Beckermann:
Yeah, I think for me also it was a little bit about, it was just easier to understand the data. So when the first triplet trial came out, I got it. I understood triplets were going to be a thing and could use ZYTIGA-Pred, but when ARASENS came out I was like, there’s clear separation of the curves, there’s no question about the data. So I think in addition to the toxicity profile, I felt really confident in the data itself.

Dr. Morris:
And I think it’s come up already once this evening kind of talking about some of the newer things that have been, you mentioned ESMO and over the last several months there’ve been several reports out, not necessarily US-based trials, but there was one including darolutamide in a different disease state that we don’t currently have available here in the US for doublet ARANOTE trial. You guys obviously probably paid attention to ESMO.

Kind of summarize kind of your experience at least looking at that data on how it might influence what we could do down the road if something was approved as a doublet versus a triplet with darolutamide?

Dr. Tan:
Yeah, I think amongst all of the ARSi’s, so enzalutamide, apalutamide, darolutamide now, also abiraterone/prednisone if you look at the hazard ratios, they’re all very similar as far as survival or RPFS.

Darolutamide does not have a survival advantage yet, but I think longer follow up we may see that, the hazard ratio I believe is at 0.82 currently. So we just probably need longer follow up, but I think probably a lot more similarities than differences in the efficacy.

Dr. Morris:
Any other just summaries from the data from ARANOTE, people watching may not have seen the presentation. Kind of summarize what you at least understand about the ARANOTE trial. None of us participated, it was an ex-US study, but doublet therapy with that versus monotherapy ADT, which was the reason this would not have been ethical in the US where we have options available. But if you guys could just summarize for somebody that had not seen ESMO, what was your main takeaway from that other than the fact that it looks similar for PFS? Anything else we need to be anxious about based from that data or should we wait or does it even matter?

Dr. Beckermann:
No, maybe just to summarize the ARANOTE study. So as you already mentioned, kind of ex-US population. So one thing that was a little bit different about that is a higher proportion of patients that we don’t sometimes get on our other trials. So it’s 30% patients Asian, 10% African American. And the other things to highlight was about 70% I think of those patients also were metastatic de novo.

So again, as Alan has said, continue to show that radiographic percussion-free survival that we expect when we partner an ARSi with ADT. And I think the hazard ratio was like 0.54.

It was different than TITAN, which was the Erleada. So in TITAN that trial had a dual primary endpoint of PFS and OS. So maybe that’s why we’re not seeing the OS yet. It’s just because the OS events are not mature. But really looking down the forest plot benefited everybody.

So I think what was really great to me about this trial was I don’t know that I needed any more solidification that darolutamide is a good drug or that we need to be doing combination therapy. But just because it had been a little while since we’d had one of these trials, I think it kind of brought back into the popular conversation so that hopefully we’re encouraging that there is benefit OS PFS time to castration resistant, like all of these points that we know, as you were mentioning before it gets real that this combination is helpful.

Dr. Morris:
Dr. McDuffie, another one that was recently released, PEACE-3, another one that included this is a partnership. And so walk through for those watching what the PEACE-3 trial, if you feel comfortable doing that, what kind of it was designed as and what it was looking at and what we should take away from conditions?

Dr. McDuffie:
A patient population that previously treated, if I’m not mistaken, that received radium-223 plus enzalutamide versus enzalutamide alone in relapse. And what we saw was a benefit in OS for the radium-223 enzalutamide group compared to the enzalutamide alone group.

Like the study, I think that honestly in clinical practice it’s going to be a little bit difficult to find that exact patient based on the trials that we have spoken about earlier because a lot of patients are now getting triplet therapy. So it’s a very nice piece and I think in the armamentarium to have, I think I struggle as a community oncologist to find where I would exactly use that. Plus I also have to send my patients some distance to Nashville in order to get radium-223.

I will say backing up to the previous two studies, one of I think strengths to just expound upon what they were saying as a community oncologist is when you see multiple different types of tumors, we like to keep it simple.

We don’t want to have to say for this screw, I need a flathead for this screw, I need a Phillips. We want kind of a one-size-fits-all. And so I think with the previously mentioned trials with darolutamide, one of the nice things is it enters that doublet space. It makes it very simple for community oncologists knowing that whether I’m using a triplet, a doublet, high-volume/low-volume disease in either space, I have a drug that I’m comfortable with and one that’s effective and works. So that was my understanding of piece three, but also my step back, my step-back thoughts from a community doctor of why those two trials put together make a lot of sense.