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Alicia Morgans: Hi, I'm so excited to be here at GU-ASCO 2024, where I have the opportunity to speak with Dr. Benjamin Lowentritt of Chesapeake Urology.

Thank you so much for being here with me.

Benjamin Lowentritt: Thank you for having me.

Alicia Morgans: Wonderful. Well, you do so many of these real-world analyses and have presented another here at GU-ASCO. This is the PROMPTS study. Can you tell me a little bit about this analysis that was investigating patients with metastatic hormone-sensitive prostate cancer?

Benjamin Lowentritt: Thank you. Yes, this is really exciting. Even though this is a new name for the study, the PROMPTS study, it's actually a continuation of some work we've been doing that's been presented previously at previous GU-ASCOs and the AUA. It's a growing data set from a number of community urology practices, from data extracted from the EMR for patients with mHSPC who are starting on therapy.

Specifically, what we presented this year was a look at those patients who go on ADT with enzalutamide and those who go on ADT with apalutamide and seeing if we can see a difference in what we can get out of the EMR. The easiest thing to get out of the EMR typically is the PSA and the PSA response. So specifically, we were looking at the patients who are achieving a PSA90 and how quickly they were getting to a PSA90. That has been shown to be a marker for a better response when patients have a deep and quick response to therapy. So it's an interesting data point to look at, and we are able to now have about 800 to 900 patients in each arm over the last four to five years since the drugs have been approved in that space.

Alicia Morgans: That's fantastic. Now, can you tell me a little bit about this data set, though? Is it urology practices, medical oncology practices? Is it a mix? How many patients, more or less?

Benjamin Lowentritt: So this specific data set is just community urology. Some of them do have medical oncology embedded, so to speak, but these are primarily urology practices. And the total data set now is well into the 15,000 to 16,000 range. When we try to do everything we can to just get the patients that we're looking for as far as the... And that's 15 to 16,000 prostate cancer patients. When we really are just trying to get to those patients who are mHSPC and are at the start of their therapy, there's a lot of work that we do to try to clean out any of the noise that's there. Plus, we then mandated that we had at least a year's worth of follow-up on all of them. So to get to that point, we got down to about, like I said, about 800 to 850 in each arm of the group that had apalutamide, the group that had enzalutamide, and then could compare them.

There was some weighting that was done to normalize for some very minor differences in racial and other factors to try to normalize them. But since the data set has gotten bigger, we've had to do a whole lot less of that weighting and really are getting to data that's as clean as you could hope for when you're talking about real-world evidence.

Alicia Morgans: Well, and that's why I love talking to you because you work in this type of data all the time, and there are some inherent challenges that if you're not really conscious of those, if you're not doing the weighting, if you're not pulling that together, then you may miss them. And actually, 800 in each arm is a really large number when it comes to real-world evidence because of the complexities of this data. So, that's great.

Benjamin Lowentritt: And we've looked at other data sets too, and going forward, the hope is that we're going to actually have claims data to match with this and then really can get deeper into some of the outcomes. Because clearly, we're looking at a very specific question, a very specific timeframe within the disease, so there are going to be holes in what we can really deduce from this. But what was really interesting from the data, and this is something that we've now seen repeatedly, is there does appear to be a difference. And when we saw those patients with apalutamide and those with enzalutamide, we see a more rapid response in the patients on apalutamide and a persisting difference in how many people get to that PSA90. Overall, about a 20% difference in the likelihood of getting there.

So that is an interesting point when you see this because reality-wise, we're not seeing a lot of head-to-head trials, those are hard to do, and this would require following people and getting support for that, etc. It's practically a difficult thing to do. So using real-world evidence to get to some of these questions that are difficult to answer otherwise, or at least suggest that there could be something that we want to look into or help inform clinical practice, it's been a very interesting journey to do it. But there is a lot of work to make sure that the data is as appropriate and clean, so to speak, as you can get it.

Alicia Morgans: Well, that's great, and it's so interesting to hear about that difference. Now, I know that the data does not show this because you're not digging into each chart and really understanding on a patient level the reasons that could be contributing to this, but do you have any thoughts about why there might be these differences? Is it related to dose reductions of enzalutamide? Is it related to discontinuations or pauses in therapy? Is it truly potentially inherent differences between these molecules? Maybe it's all of the above or maybe it's something else that you're thinking about. What do you think, again not from the data, could potentially be contributing to this?

Benjamin Lowentritt: No, you bring up all the likely reasons why. But I do think when we looked at this, the patients did need to stay on therapy. So these weren't discontinuations necessarily, and certainly if a patient switched therapy they were taken out of the data set as well. So we're looking at those patients that were able to, at least from what we can tell, stay on therapy.

Now, what we can't tell is, were they reducing dose? I do think that may be a component. Were they skipping doses? Were they having dose interruptions during it? I think that's a possibility in the difference that drugs may be tolerated. There's also the possibility that despite the fact that we think of them as similar mechanisms, they are different. And they are different drugs, so they could be behaving differently in how they're working within the patient. But I do think there are these limits to what we can deduce, and so we have to be careful about that.

But you're absolutely right that when we have these types of signals it leads you down this road of wondering. My bet, if I had to say, is that it is some degree of dose reduction, maybe some degree of dose interruptions, and the ability just to stay on therapy throughout the whole time and stay on full dose. But that is my personal bias, etc., at this point. But it's not something we've been able to prove yet.

The hope is maybe with claims data, we can see more readily are patients, you might be able to get more in-depth information on how frequently they're filling medications and other things so that we can get to some of those questions as well. So we'll see.

Alicia Morgans: Well, I think to your point, these are really ways for us to better understand what's happening in our practices and it raises all these questions that we can then investigate further. And so I appreciate you kind of going through that thought exercise. And again, just for anyone listening, this is neither your opinion nor... These are both opinions, I guess I should say. This is not coming from the data, but these are our hypotheses about what could be happening here.

Benjamin Lowentritt: Absolutely.

Alicia Morgans: Ultimately, this is what we found, or what you found I should say. And how does that affect your clinical practice? What does that do when you're trying to take care of patients with metastatic hormone-sensitive disease and you recognize that there may be differences in some of the drugs that we have access to use?

Benjamin Lowentritt: I think fundamentally, and I think we've lost some degree of this in some of the discussions around PSA and the limitations of PSA as a marker, I do want to just highlight that we know that PSA90, and we've separately reported on achieving an undetectable level PSA as determined as less than .2, that that is actually a very important prognostic marker in helping understand the likelihood that patients are going to have a prolonged response and have good overall. And that comes from the randomized trials and from numerous different randomized trials. So that is an important marker. And I think I do use, for those patients who get to a very low PSA, a PSA90 or a PSA less than .2, I do use that in how I curate specific protocols for following them, for monitoring them.

Typically, I'll see these patients every month to two months early on to make sure they're tolerating it and make sure they're responding. But to be able to see them quarterly and maybe coincide their visits with when they're getting their ADT injections instead of having to see them extra visits in between is actually a meaningful improvement in the patient's day-to-day month-to-month existence with their disease. So also just being able to counsel them on that. So there's the reassurance when they do get to that level. There's also, for those patients that aren't getting to that level, I'm a lot more likely to watch them more closely and look for some of the other biomarkers and other things that might guide us towards another therapy going forward. I think you have to understand that very well.

As for the differences that we see, I do think that it's really more the overall experience, but this data supports it. We talked about other things that the data may be reflecting, including tolerability and other things. I still think those are more important in how I assess what drugs I might choose. Drug-drug interactions are still important. Financial, insurance, that still drives a lot of the decision. But this data does help inform clinical practice in what you might expect to see in a community urology setting. And that's how I've approached it. And when I talk to patients about their options I do now start to layer in that, hey, there's some suggestion that there may be a difference. And most patients are looking for anything that could help guide them that way. So it does certainly start to inform your practice.

Alicia Morgans: I really appreciate you thinking through that, and I love that you are using that for patients who reach that level as a way to reassure and think about how you might back off slightly in terms of the frequency of visits. That's a win for patients, and it really does, I think, help them have that hope that they're doing well. And I do the same in my practice, and I think it's really worthwhile.

So if you had to share an overall message with the listeners on this work and on the compilation of information you have around the way that these drugs can help us achieve a PSA90, an undetectable PSA, what would your message be to listeners?

Benjamin Lowentritt: I think there are all these discussions about what options and how amazing it is that we have all these newer options over the last 10 years for prostate cancer, and that really is true. We've had some of these discussions before and I think it's something you've been very helpful in, is we have to understand the consequences of using some of these medicines as well beyond the prostate cancer and what they affect in their general health, etc. And I think it's that much more important to make sure that we're getting the responses that we want when we are treating aggressively like we are with these intensifications of therapies. I'm very curious whether or not patients that maybe have these excellent responses, there was some discussion at the conference about this, about de-escalating at some point. And I have mixed feelings about that. I mean, that's a whole separate conversation.

But as for the take-home message today, I think given what the goals of therapy are for the mCSPC patient, looking at this kind of data in the real-world setting can start to give a picture of what we're achieving beyond the clinical trials. And I do hope that we're beyond the days of ADT alone and people are using these therapies to really help our patients because we know the benefits that are there. And it's exciting to be able to share data that shows how many patients are really having a great response.

Alicia Morgans: Well, thank you for sharing that, and thank you so much for being really a leader in the urologic oncology field in terms of helping us really hold that mirror to our practices, to ourselves, to our community, to help us understand where we are so that we can take those next steps and get to where we want to be in the future. I sincerely appreciate your time and your efforts.

Benjamin Lowentritt: Oh, thank you so much. Thank you for having me here for the conversation. I appreciate it.