Martin Schoen: Thank you very much, Dr. Agarwal. Pleasure to be here.
Neeraj Agarwal: So we enjoyed your presentation at the 2026 American Urology Association meeting in Washington DC on the real world study using a urology database comparing enzalutamide versus apalutamide in patients with metastatic hormone-sensitive prostate cancer. So first of all, congratulations-
Martin Schoen: Thank you.
Neeraj Agarwal: ... on this meaningful study. Could you tell us more about the study methodology first, starting with the primary endpoint, and then we can talk about the results?
Martin Schoen: Definitely. Well, we wanted to really understand how do we treat patients with metastatic hormone sensitive cancer and what is the best drug that is out there? And there have been prior studies that had compared apalutamide and enzalutamide that showed some differences, but we felt that it was appropriate to use what we consider as a target trial framework, where we enroll patients very similar to what a clinical trial or a prospective clinical trial would have done, where we limit the inclusion to patients who are started on therapy within a narrow period of time similar to the ARCHES trial or TITAN trial. So we wanted to really use the best methods possible to try and see if there is a difference, because we feel it's an important question to personalize therapy as much as possible.
So what we did is we used the urology database, which is the PPS linked to the Komodo claims to try and understand the outcomes. We were able to identify over 4,000 men that were treated with both apalutamide or enzalutamide, and we limited the inclusion to patients who were started on their therapy within three months of their diagnosis, therefore limiting some of the biases that occurred, because enzalutamide has also an approval for metastatic castration-resistant disease and apalutamide does not. So we were able to match patients with one-to-one between the two groups and were able to include over 1,700 in each arm. So it was really a robust patient population of over 3,500 patients that we included to be able to look at the key outcomes of overall survival, time to PSA progression, time on therapy, and also time to next therapy.
Neeraj Agarwal: So a pretty large database from more than 3,500 patients?
Martin Schoen: Yes.
Neeraj Agarwal: That's three times larger than most of the registration trials with each one of these ARPIs. So please tell us more about the data.
Martin Schoen: Yeah, the patients were approximately 73 years old in both arms. They came from all across the country, and they were treated in the last five years, the majority. We were able to have a median follow-up across all of the arms of over 22 months, so almost two years of follow-up. And some of the patients were followed up to that four to five year period of time. They had very similar Gleason grade as well as other disease features such as PSA after we performed our matching in our target trial emulation dataset.
Neeraj Agarwal: And what were the results?
Martin Schoen: Well, interestingly, we actually found no significant difference in the overall survival, really no significant difference in time to PSA progression, nor no significant difference in treatment duration. So really we found that when we used this methodology, we could not identify any differences between these two drugs in this dataset.
Neeraj Agarwal: Just for our quick recollection, we are talking about ADT plus enzalutamide versus ADT plus apalutamide simulated trial, if you will, because you are selecting these 3,500 patients, more than 3,500 patients, which actually meet the predefined criteria as if they are clinical trial candidates. Only difference is you're going back and looking at them, but they are eligible for this targeted clinical trial the way you are defining it.
Martin Schoen: Yes.
Neeraj Agarwal: And they must have started either enzalutamide or apalutamide with ADT within that defined period. So there is no imbalance from that perspective that some of the patients started enzalutamide six months before or apalutamide a day before, because that could potentially induce a huge imbalance in the outcomes. So with those stringent criteria, you are finding that there is no difference in time to PSA progression or overall survival or other secondary endpoints between enzalutamide and apalutamide. Is that correct?
Martin Schoen: That's exactly right, sir. And that you know as a trialist and many of us who pay attention to these sorts of studies would know that patient selection is key. Whether you're trying to find an outcome in a prospective trial, you really need to figure out who are the patients that are most likely to benefit and how do you really identify the patients that are appropriate? It's the same in retrospective research, that you really want to select the patients who are similar to each other, that are most likely to benefit, that you're really trying to find the effect.
And when you include patients that started on a drug maybe 18 months later or 12 months later, which would never have been included in some of the subpivotal phase three trials, it really induces a bias and it's hard to use statistical methods to account for those underlying patient differences. That's why we feel a framework of what we consider the targeted trial framework, which is out there as it was just a publication in the JCO is one of the best methods for doing real world research, is to really select patients appropriately, and then you don't actually have to do as much statistical matching as well as machinery to be able to account for bias, because the patients are very similar at baseline.
Neeraj Agarwal: And none of those statistical methods are foolproof.
Martin Schoen: Definitely not.
Neeraj Agarwal: There's no way to fix all the biases. It doesn't matter how good your tool is. So I'm so glad you have embarked upon this initiative of conducting retrospective studies in a most rigorous fashion, if you will. So just to conclude, enzalutamide and apalutamide were equally efficacious?
Martin Schoen: Yes. In this population, which simulates a trial, there was no difference in any outcome that we looked at and we found that the drugs are incredibly similar in all of their characteristics and we could not find a difference in the two-
Neeraj Agarwal: And both are very effective?
Martin Schoen: Incredibly effective. And the median survival was not reached during our period of time where we analyzed, showing that we are actually even getting better outcomes than some of the pivotal trials such as ARCHES and TITAN, that median survival was not reached during our follow-up period.
Neeraj Agarwal: That's wonderful news for our patients.
Martin Schoen: It is.
Neeraj Agarwal: And that basically reinforces the idea that everyone should be getting at least a doublet therapy of ADT plus an ARPI and nobody should be getting ADT monotherapy unless there are obvious contraindications. And there may be one or 2% of patients out there, but everyone should be getting at least ADT plus an ARPI.
Martin Schoen: I agree and that especially in these patient populations that have high-risk disease, that we really should be doing combination therapy with an ARPI as our backbone. And as future trials will tease out, what even further additional agents do we need to add onto that versus for certain high risk features?
Neeraj Agarwal: We look forward to looking at those new research projects from you. They're always so informative and they help us in decision making in our clinic. So congratulations, Marty, for another great presentation at the AUA meeting and we look forward to the full manuscript in the near future.
Martin Schoen: Thank you very much, Dr. Agarwal.