Phillip Koo: 

So now let's move on to advanced disease. So, disease out, now that is metastatic, has spread outside of the prostate gland. And some of us may have heard of a study called ARANOTE. And I believe there were some new data presented around this study called ARANOTE, so can you help fill us in here as well?

Zachary Klaassen: 

Yeah, so this was in patients that had metastatic hormone-sensitive prostate cancer. And that means that they have metastatic disease outside the prostate. They may have had treatment previously, and we call that metachronous or recurrent metastatic hormone- sensitive disease. Or they show up to the clinic, they've had no treatment, and this is the first stage that they get is this metastatic disease. That's called de novo metastatic disease. So, both patients are kind of grouped into this metastatic hormone-sensitive prostate cancer umbrella.

We've had a number of what we call second-generation ARPIs [androgen receptor pathway inhibitors], which are pills that help in combination with ADT, which is the hormone therapy, improve outcomes in these patients, whether they're recurrent or they show up with metastatic disease. And ARANOTE was sort of a second study of darolutamide, which is one of the ARPIs, and there's now four of them, that was looked at in a previous trial where we combine darolutamide, plus Lupron, plus docetaxel. So, it's called triplet therapy, and we still use that in a number of high-risk patients for sure, hitting that tumor hard. 

ARANOTE was the second study looking at: what's the combination of darolutamide plus ADT? Does that improve outcomes versus ADT alone? And so presented at ESMO in 2024  -  was presented by Fred Saad-  and showed a 46% improvement in recurrent [editor’s note: radiographic] progression-free survival compared to ADT alone. And so, we kind of expect that result, but it was a nice take-home point that this combination by itself without the chemotherapy works better than ADT.

And so, it now gives patients a very tolerable option with darolutamide plus ADT to bring their prostate cancer under control very quickly. And to your point, what was presented at ASCO and sort of why I wanted to lead into this is two important things. One, right at the end of ASCO, June 3rd, 2025. This was FDA approved. So, this was presented initially, September 2024. Fast forward to June 3, 2025, it's now FDA approved as a combination of darolutamide plus ADT for these patients.

Alicia Morgans presented some really interesting quality of life data. And so, when we have these patients, we're obviously thinking about the cancer control and what's the best option for them, but what's the tolerability going to be? How much of an impact on quality of life is this going to have? And so, there was two important end points she showed.

There was a 24% improvement in time to pain progression. So, we know that patients that have disease that's in the bone, this can be painful. And so, this combination got better control of that pain compared to the ADT monotherapy by itself. And it also improved by 28%, time to deterioration in quality of life.

So if you think about this on a high level, we're controlling the cancer better, we're decreasing their time to where they have pain, and we're decreasing the time to where their quality of life decreases, I think that's a triple threat because we have both the quality of the life aspect and we also have the cancer control aspect.

Phillip Koo: 

You know, that's great to hear, and I think it's wonderful because we often lose sight of some of the negative effects or adverse events that these drugs can cause, but it's great to hear some of these regimens and therapies improving quality of life, which we see here as well.