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Alicia Morgans: Hi, my name is Alicia Morgans, and I'm a GU Medical Oncologist and Associate Professor of Medicine at Northwestern University. I'm so excited to have here with me today, Dr. Mike Cookson, who is the Chair of Urology at the University of Oklahoma. Thank you so much for being here.

Michael Cookson: Thank you for having me.

Alicia Morgans: Wonderful. I wanted to speak with you a little bit, Dr. Cookson, about a presentation that you and your team had at ASCO 2021. We really looked into understanding age subgroups in the HERO trial, and trying to understand whether there were differences in castration rates between patients with different ages. Can you tell us a little bit about it?

Michael Cookson: Yeah. Obviously, this was a subset analysis of a previously published study, the HERO study, looking at the value of a new oral agent, relugolix, as compared to traditional standard androgen deprivation therapy with leuprolide. And so, what we were looking at, though, was whether or not there were any differences in the way that patients responded to the therapy based on their age, so we were looking at efficacy first, and then secondarily, we looked at things like, well, do they have any different adverse events? And then, also, there's a unique part to this study, where there was a look at when you stop the therapy, how the patients recovered from that therapy. And so, we were looking at, is there any difference in any of those three areas with respect to patients looking at their age?

Alicia Morgans: Well, this is certainly a really important aspect of clinical practice. The median age of diagnosis of prostate cancer is certainly in that older adult category, I think it's around 66 or so. And certainly, when we're using hormonal therapies, we know that those are actually more commonly used in older men, both because it may be a more advanced disease, then also because people don't necessarily always want to do surgery on them, so sometimes they have it in combination with the radiation or even, unfortunately, sometimes primary ADT. I'm just wondering, what exactly did you find in terms of rates of castration and then your adverse events?

Michael Cookson: Yeah. Of course, as you mentioned, this is a disease of aging men, and so most of the patients in the study were older, but about 20% of the men were 65-years-of-age or younger. And so, that 20% was an important cut point, so we looked at above or below the age of 65, and we also looked at 75 as a cut point too. About 71% of the patients were 75 years or younger.
What we really found was that in terms of the ability to lower the testosterone and to sustain that level of lowering, there wasn't any difference based on their age. Patients responded well, regardless of their age. In the bigger study, the relugolix was effective in lowering that testosterone, kept it suppressed more consistently for the time period that the study was looked at, but it didn't really matter about the age. So, that's one thing, is that the patients responded well regardless of their age. The other thing to note is that at least in terms of the adverse events, they seem similar and were not really different based on their age. So again, similar efficacy and similar in terms of the side effect profiles based on age.
Probably the most interesting finding was the recovery part. And so, as you mentioned, there are men who go on these androgen deprivation therapies, and radiation's a good example. There's a defined time that they're going to be on that therapy, and during that therapy, they do have side effects from their treatment, hot flashes and fatigue, and lots of different ways in which it affects their quality of life. What this study found was that once those men come off of the therapy, the patients in the oral agent were able to recover much quicker, and the most impressive recovery was in those young men who were less than 65. So, if you looked at that, and I've got my poster handy, so I won't miss speaking about the data, there was a significant recovery in those patients. And so, somewhere around 90% of those young men, really, the age 65 or younger, they got a relatively rapid recovery of their testosterone.
Those are things that we think about in that niche group where you're treating a younger man, he is a defined period of time on the therapy, it's beneficial to his cancer outcome, and he wants to recover from that as quickly as he can. And so, that's really the major finding of our subset study, is that younger men bounce back quicker and have a more rapid recovery of their testosterone once that suppression's no longer needed.

Alicia Morgans: That's really important too. I think I was emphasizing the older adult population, but, as you mentioned, there are a lot of men who have aggressive disease who are actually younger men and they have different priorities sometimes and that testosterone recovery can be very high on their list. So, that's super important and I really appreciate you bringing that to light. If you had to summarize this work to really just have a short statement about what people should take home from your study. What would that summary be?

Michael Cookson: If I was going to summarize what we found, what I would say is that the first thing we looked at was the ability for relugolix to create that, compared to leuprolide, to create a sustained lowering of their testosterone level. What we found was that, as in the overall study, that it performed better and that was independent of age. So, if we were to look at subsets of, say, younger men, say those 65-years-of-age or less, there was about a 91% sustainability of the treatment as compared to about 84% in the leuprolide, but not statistically different. So, it is a sustainable thing and it works regardless of age. If we looked at the adverse events, the side effect profile, again, similar findings regardless of age, no real differences there.
Where we found our significant finding was in the recoverability of testosterone once the therapy is stopped. There was a subset, about 19% of men, who were 65-years-of-age or less, and in that group, when we stopped therapy and we look at the recovery in the first 90 days, that's where we found about 79% of those men recovered their testosterone, compared to only around 17% in those patients that were treated with leuprolide. That's a pretty significant finding and that's really the emphasis of this poster.
This new therapy, this new oral agent, works regardless of age, so that's an important thing, and the side effects are present regardless of age as well. But when we're looking at the recovery of testosterone, we're going to see a more robust recovery in men that are younger, say 65-years-of-age or less, and that can be really important for those men are treated for a real defined time, such as when used in combination with radiation therapy, or for those men on intermittent therapy, where they want to recover some of those quality of life issues once the therapy has stopped.

Alicia Morgans: Fantastic. Well, I sincerely appreciate your time, and of course, the work that you and the team have put into this analysis. Thank you so much.

Michael Cookson: Okay, thank you. Thanks for covering us.