Zachary Klaassen: Hi, my name is Zach Klaassen. We are at AUA 2025, in Las Vegas. We are on UroToday, talking to Dr. Ben Lowentritt, Chesapeake Urology. Today, we're discussing a real world experience, looking at apalutamide versus enzalutamide in Black patients with metastatic hormone sensitive prostate cancer. Ben, thanks so much for joining us again.

Benjamin Lowentritt: Thank you for having me. It's great to talk to you.

Zachary Klaassen: So just talk a little bit. We know there's underrepresentation of minorities in trials. And this has been a huge issue not just in urology, but at the FDA level across all malignancies. Why is it so important to have representation of the patients we're going to be treating?

Benjamin Lowentritt: Now, obviously, it's a key thing. Many of our trials that lead to approval in the US are still international trials. And although in the US it's really well known-- the higher propensity to get prostate cancer in the African-American population and the higher severity. It's not that population isn't there across the world.

So oftentimes, we see a percentage of African-Americans in the 5% range or maybe less in our big trials. That's not what we see, where it's probably three to four times that in the US population. And for many of us that practice in urban environments, it's an even higher number that are having the advanced cancer. And so we are always trying to learn. Do we have a difference in this population?

Historically, we know that it's been a more aggressive disease. Are our treatments as effective? Are they potentially more effective or less effective? So I think there's going to be a limit always to doing a traditional prospective, randomized, double blind trial to show that. This is an area that screams for the big data approach, and trying to bring in more data to really understand it.

Zachary Klaassen: And you guys have done a great job with your group, looking at some of these really sophisticated databases just to tease some of that out. So just set the stage for the trial design you presented at AUA.

Benjamin Lowentritt: Yeah, this is actually a offshoot of a project that's been going on for a number of years that's grown and grown in size and complexity, where we're able to pull in clinical data from EMR systems using a largely community-based urology data set through PPS, and now pairing it with a large well-known claims-based database called Komodo. And we use the two of those in the same patients to both show outcomes like PSA response, but also survival. And we're getting to cost data and other things in the future.

So it has really been exciting to take those and put them together. And this was within the group that we've been developing over a number of years-- pulling out those African-American patients and seeing, are the outcomes that we saw in the broader population true in that population as well?

Zachary Klaassen: And so this study looked at specifically, ENZA and APA for metastatic castration sensitive. What did you guys find? What were the key take homes?

Benjamin Lowentritt: Yeah, so when we look at what's been happening over the investigations we've been doing, we've seen a couple of different things. First off, if we're just looking at apalutamide, we're seeing that the response mirrors what was seen in the TITAN trial, which is really great to see that we're seeing those kind of outcomes.

The specific outcome in this study was looking at PSA90 or a 90% reduction in PSA, specifically at the six month interval from initiation of therapy. The nature of real world evidence like this and the data approach, is that you have to get a really defined outcome like that.

Zachary Klaassen: Yeah, like a landmark.

Benjamin Lowentritt: Right.

Zachary Klaassen: Yeah.

Benjamin Lowentritt: We also did look at it over time. But that's more exploratory. And so looking at that six month, we saw-- which is considered a rapid response at six months. And also a PSA90 would be a really deep response. We saw excellent patient performance at that point.

In the comparison, what we see is that-- and we've seen this across a number of different data sets, both in the urology and medical oncology world, but specifically, in this one looking at PSA90-- looking at the African-American population. We saw that the apalutamide patients outperformed the enzalutamide patients by achieving that PSA90 at six months with an overall hazard ratio of 1.42, or in this case, the higher number being better. About a 42% increased likelihood of getting to a PSA90 at six months. So it was great data to see and really impress.

Zachary Klaassen: It's a pretty significant finding, isn't it?

Benjamin Lowentritt: Yeah. I mean, it's one of those things that you scratch your head the first couple times you see it. And then you have to believe it, I think, at a certain point. But one of the important things about real world evidence is it's not prospective. It's not randomized. It is weighted in a way to try to remove bias. And we spent a lot of time doing that to make sure that as much as we can we were removing any bias. But it doesn't tell us why this is happening.

Zachary Klaassen: That's right.

Benjamin Lowentritt: And so I think, whether it's-- there are all types of variables. And I'm just guessing. It could be about patient tolerance. If you're not able to take the full dose, or they're not able to stay on it as long, or take it every day. It could be about cost, or some affordability issue, access questions. Those are things that we haven't figured out how to pull out of this type of data set yet. But in the all comers. Here's the experience. Here's what's really happening in our practices. This is what we found.

Zachary Klaassen: And I think, too-- I mean, we always talk about this. There's not going to be head-to-head to comparisons. And they're certainly not going to be head to head comparisons in minority patients. And you practice in mid-Atlantic. I practice in the South. We have a huge population of African-American patients that either have de novo recurrent metastatic hormone-sensitive prostate cancer. So based on this data, you're sitting down with an African-American patient. What's your conversation like? How is that maybe changing based on this data?

Benjamin Lowentritt: Yeah, I think, this is one of those things that enters into the equation. There are a number of different reasons why we know people choose different medications. And we have the wealth of options here in the mCSPC world. But this is one of those things that weighs heavily when I'm saying, OK, if we're going to do doublet therapy, and we're looking at one of the ARPIs, this is one that I have real confidence in the response that you're going to have.

I also think that it's important to understand that if you get to that PSA90-- if you get there earlier-- and we have similar data on getting to an undetectable level of 0.2 or less in the same cohort. These are patients that we know from other data respond longer, and have a better overall survival picture. And we know that from some of the prospective studies.

So it gives us that confidence to say, hey, we hopefully are going to get a better outcome. And if you're in this group, we might even be able to watch you a little bit less intensely. We may even down the road be able to consider things like deintensification. And so yeah, it is an important part because this PSA as a marker has troubles, as we all know. But the depth and speed of response has been shown to really affect overall, or to be a predictor of overall survival.

Zachary Klaassen: And these are operational things that patients understand. At six months, we have a time point. PSA90, we can explain what that is. This is what we're shooting for based off of this. And we'll go from there.

Benjamin Lowentritt: Yeah.

Zachary Klaassen: Great conversation. Great data. Any quick take home messages for UroToday listeners?

Benjamin Lowentritt: Well, I think what's exciting about this data is that we have continued to find ways to go in new directions. And we will go in more. This was really great to look at a subset of patients that, as you said, we don't get to look at probably as easily in prospective trials.

I think we're going to be able to get to some cost data coming soon, and really, just generally getting into some of these questions that are not easy to find out, some of the comparisons. And then, I think, eventually, we want to get to some of the deintensification and some of these other issues as we get numbers to support that.

Zachary Klaassen: Absolutely. Ben, always enjoy chatting with you on UroToday. Thanks for your time.

Benjamin Lowentritt: Thank you very much.