Martin Schoen: Thank you very much. It's an honor to be able to talk about our work in veterans using data from across the country to hopefully understand how this life-prolonging therapy is helpful.
Kristine Lacuna: Absolutely. So just to get us started, can you tell us a little bit about the background, the reasons for why you decided to look at this population, specifically this drug? I think it's a really interesting time to be looking at radium-223, especially in patients where we're seeing real-world data. So please tell us a little bit about the study design and how you came about to the way that you're looking at these patients.
Martin Schoen: Definitely. Radium has been available for many years for patients with CRPC, but as there's more and more variety of therapies available, we wanted to see what is actually going on in the real world. And especially as there's new data such as PC3 that shows the efficacy of radium, again, in a newer population. We used the VA national database to identify patients over the last 10 years that received radium. We were able to find 661 patients, so a decently sized population. The median age was 73, and so it's a little bit older than the ALSYMPCA population. We wanted to find who's actually receiving it and get information about that. The other thing is that we found that there was approximately 24% of African-American patients that received radium, which has not really been seen in other populations. And we wanted to show what are the outcomes in these veterans that are receiving radium, and be able to really show the duration of therapy as well as their overall survival.
Kristine Lacuna: Right. No, I think that's wonderful. I mean, I think when we look at large phase-three randomized trials, these patients don't always fit what we see in our clinic. And so it's really great to hear that there's real-world data, the VA population where we have such a large population that we're looking at, and important to hone in on the differences. So you had mentioned that you looked at overall survival. You also looked at some patient characteristics, including baseline PSA, age, race, which is what you discussed. Would you be able to delve deeper into what you've found in terms of age, in terms of race, in terms of the baseline PSA and some of the other things that you looked at in comparison to what we're seeing in the large phase-three study?
Martin Schoen: Yeah, definitely. And so I really think that real world evidence is able to give us almost phase-four data to say-
Kristine Lacuna: Absolutely.
Martin Schoen: ... how is it actually being used? And so yes, our patients were a median age of 73, which in the ALSYMPCA trial is around 71. Median PSA was 50, which is relatively high. It's used in this later-line setting. Our BMI was about 29, which is also a little bit higher than the population, and then slightly higher rate of comorbidities as well. And as said, we only had a 24% Black population, which is important to show that there is efficacy in a more diverse dataset. And this definitely, I think, reflects a lot of the VA practice where patients who maybe have lived maybe a little harder life or had military exposures such as in Vietnam with Agent Orange, that's in this period of time, there will be many of Vietnam vets who would have prostate cancer and then receive therapy, so it's really important to test this.
Kristine Lacuna: Yeah. No, I think that it's really important to hone in on those differences. And when you're talking about the ALSYMPCA trial, this was a large phase three study looking at the addition of radium-223 in patients versus placebo for those who either refused docetaxel or received docetaxel. And we're seeing about a 14-month difference versus an 11-month difference. So do you think that some of those characteristics that you talked about are contributing to that difference? I know it's hard to compare cross-study, but honing in on the differences between overall survival, do you think that that has anything to do with what you studied age and, perhaps, those comorbidities that you talked about?
Martin Schoen: Completely. I think what's at play here, whenever you're looking in the real world, you're looking at a broad patient population that is not selected for inclusion. Whenever you go through a selection process, you're always identifying patients that are a little bit more favorable or that can come to an academic center.
Kristine Lacuna: Absolutely.
Martin Schoen: And so our median overall survival in the entire cohort was 11.2 months, which is a little lower, but that should be expected on any real world study. I will add that of the patients who received genetic testing, so these are patients that have been treated more recently when genetic testing is available. Our median overall survival was closer to 14 months, which is around what the ALSYMPCA data showed. So showing that over time, things have actually improved, and possibly even the outcomes are better or at least preserved in this patient population.
Kristine Lacuna: Absolutely. And I think that that's a really important point when you talk about the genetic testing. So in your study, I think it was really great that you looked at tumor suppressor gene mutations and looking to see if there's any difference for patients who express PTEN loss, RB1 loss, or TP53 mutations, because we know classically these patients unfortunately have a worse prognosis, are more prone to developing neuroendocrine disease. Did your study surprise you in terms of the findings of efficacy when you're looking at patients who had one of these mutations versus the patients who didn't have these mutations? And could you talk a little bit more about why that might be the case?
Martin Schoen: Yes, definitely. So in about approximately 185 patients, so about one third of our cohort, we had genetic data available, and half of those patients around 90 had TSG alterations in one of the three, PTEN, RB1, or TP53. My hypothesis was that those patients would have a worse outcome based off of other-
Kristine Lacuna: It makes sense.
Martin Schoen: ... datasets. Typically, the disease is more aggressive, there's more aggressive variant or neuroendocrine-type features, and therefore the prognosis is worse. We were surprised to see that there was actually no difference in overall survival in patients that had TSG alterations compared to TSG wild-type, which is impressive to see such a good outcome. And they might be because of the mechanism of action, radium does have a very different mechanism of action than any other agent that we have available. And so it's something that I feel like could be studied further to really tease out why this agent, there was no difference in TSG outcomes in the two different populations.
Kristine Lacuna: Right, right. I think that's definitely worth investigating, especially because we use radium up until recently, towards the end of a person's disease, and we're certainly thinking about radium in different contexts. Of course, we heard about PC3, the overall survival data benefit. And so I think that I would love to hear your future directions for this database. I think it's a wealth of information that we could really learn from, especially from a VA database where it's easier to get prior treatment information, survival information. I'd love to hear what your advice is for the next direction and your future directions for the trial.
Martin Schoen: Yes, definitely. I think the next steps for us is to really put it into context of the patient's prostate cancer journey to look at what are the prior treatments, what have they received? Some of the patients may not have had RPs in the hormone-sensitive space or then most of them would've had them in castration resistant. And then also based off of what prior chemotherapies they received, many of them may have received docetaxel or cabazitaxel.
Kristine Lacuna: Absolutely.
Martin Schoen: And so I think that that is where we want to go to be able to identify a population that might have the greatest benefit and what stage, and where we can put this in the treatment sequencing.
Kristine Lacuna: Yeah, absolutely. I think that that's really special to the VA database because I've worked with a lot of claims databases before, and it's really hard to extract some of those prior treatments. And I think that that's really special of the place that you're at, and I think it could really tell us something about exactly what you said, which patients would specifically benefit for this and context in ordering of the treatment. So any final words, any advice to give for us in terms of just real-world data or your interpretation of your study overall?
Martin Schoen: Well, there's one other thing is that we did look at the number of cycles of therapy that were received. And so the median number of cycles was four, and only one third of patients received all six. And so that's another future avenue to try and understand why patients may not have received all six cycles.
Kristine Lacuna: Absolutely.
Martin Schoen: And then are there things that we could identify that we could maybe improve or to be able to deliver this therapy to the right patient? What features are associated with the most benefit and the highest receipt of therapy?
Kristine Lacuna: Yeah. No, I think that that's a great point to end on because as we know with the ALSYMPCA trial, the majority of patients did receive the six cycles. It'll be interesting to know why those two cycles might have not been given for your patients and was it because of toxicity, was it because any kind of structural barriers, anything that is related to treatment? So I think that that would be a really important next step, and we're really looking forward to the data that's coming from your team.
Martin Schoen: Yeah. Thank you so much for the opportunity to show the work that we're doing for veterans in St. Louis and across the nation.
Kristine Lacuna: Absolutely.
Martin Schoen: Appreciated it.
Kristine Lacuna: Thank you for joining us, and congratulations on your abstract and poster.
Martin Schoen: Thank you.