Phillip Koo:

So let's go on to the next trial.

Zach Klaassen:

Yeah, so this is A-R-A-A-T or ARAAT. And what this is different than a clinical trial. This is real-world data. And so when we look at real-world data, we're trying to see what happens outside of clinical trials. And this, actually, was a very important study why I pulled it out because we have data from ARASENS, which tells us that ADT plus darolutamide plus chemotherapy is better than darolutamide plus ADT, or excuse me, chemotherapy plus ADT.

We also know from the PEACE trial platform that we have ADT plus abiraterone plus chemotherapy as well. And so what this really looked at was what's the benefit of darolutamide versus abiraterone. We don't really have any head-to-head comparisons here. So this is where real-world data... We have some limitations with real-world data. It's not mined as closely as a clinical trial. But it gives us a little idea, does darolutamide work as good as abiraterone or vice versa in this triplet therapy combination?

So this figure on the top left looks at how these patients are selected. This is out of an electronic medical record. And so when we get this population together, we're essentially comparing darolutamide versus abiraterone in the context of triple therapy. And so on this top right figure, figure 2, this is patients achieving a PSA of less than 0.2, and we can see that for darolutamide in the light blue versus abiraterone, the dark blue, for all time points, six months, nine months, 12 months, or anytime they're in the follow-up, they were more likely, percentage-wise, to get to PSA less than 0.2 versus the abiraterone group.

When we look at the bottom left, this is a Kaplan-Meier curve looking at time to PSA less than 0.2. So how much time does it take to go from treatment start to getting to a PSA less than 0.2? Darolutamide's in blue, abiraterone's in pink. And we see that darolutamide took a median of 6.4 months compared to 9.5 months for abiraterone. So a difference of about three months in the time to get to a PSA of less than 0.2.

And then on the right, we see amongst that darolutamide group, just the importance of time to mCRPC progression. Basically, this is stratified on PSA less than 0.2. This is the pink line. Versus greater than or equal to 0.2. This is the blue line. You can see a early separation of those curves. In fact, the median's not reached in the PSA of less than 0.2, and the median is 16.4 months in greater than 0.2. So what this tells us is if your PSA gets to less than 0.2 on triple therapy with darolutamide, you're significantly less likely to get to that time to get to that mCRPC endpoint versus patients that PSA doesn't quite get down to 0.2. Very important finding in this real-world analysis.

And so again, this is not the same level of evidence as a clinical trial, but does give us some information that in that triplet combination, darolutamide seems to be a little more effective than abiraterone, and some of these other analyses on the bottom of the screen also give us a little more information as well.

Phillip Koo:

So this is really interesting, I think. We probably can't explain why, but this data is telling us there's some sort of synergy or some sort of added benefit if you are getting triplet therapy with chemo and ADT to use daro instead of abiraterone. So we often see this type of these studies, like real-world evidence, real-world data studies, and it's kind of confusing. And oftentimes the data being used needs to be interrogated, the methods. A lot of things need to be looked at. What advice do you have for patients if they start seeing these types of real-world studies, and how does it translate into their actual care?

Zach Klaassen:

Yeah, great question. I know we have these discussions amongst ourselves as academics and providers. It's clearly a less level of evidence in a clinical trial. The reason we do these is because we probably will never see a triplet versus triplet abiraterone versus darolutamide trial. They're expensive to run, they take years, and so the field is moving so quickly that we may not ever see that comparison.

So the first is that, from a patient standpoint, the level of evidence is different than a clinical trial. These trials are being done just to give us nuances of where there may be a few differences. And so I think it's important for patients to know about them because their clinician may be basing some of these decisions off of these real-world studies. But again, you nailed it. There's limitations with them.

And so there has to be a rigorous statistical plan, has to be a forthright and honest limitation section to these analyses because they're all limited. We have no idea whether these are the exact same patients getting abiraterone as getting darolutamide. So we have to take this all into context. So it can be confusing for patients, it can be confusing for physicians, but it's being done to give us some nuance to maybe some of the differences between the two.

Phillip Koo:

And I think we're all pretty optimistic and hopeful that as time goes on and these techniques get better, the datasets get bigger, maybe the validity just continues to increase with these RWE, real-world evidence studies.