Martin Schoen: Thank you so much. Honored to be here.
Tanya Dorff: It's tremendous what you do working at the VA. These are our men who have served our country and really deserve the very best. And even more admirable is trying to do research to understand their needs in terms of their prostate cancer, which may be different than other prostate cancer and sort of meet them at their needs.
So your poster on this kind of real world, but veterans affairs world of metastatic hormone-sensitive prostate cancer, I think, is really important. We know AR pathway inhibitors have moved to that frontline setting, intensified therapy, but we've all had concerns. Not every patient might be fit enough. Patients have comorbidities.
So I'm interested in the analysis you did looking at the more sort of frail population and how doublet therapy performs there.
Martin Schoen: No, definitely. And it is definitely an honor to work in the veterans and they serve initially, but also serving to inform how we practice. And so yes, I'm blessed to be able to look across the experience across the entire nation of veterans that have metastatic hormone-sensitive prostate cancer.
And we really wanted to answer that question of patients who are elderly, frail or have high comorbidities, does the combination therapy of ADT plus an ARPI really associated with benefit in patients that were not really part of the pivotal clinical trials?
And so we have a prior poster that showed that in the entire population there was a benefit of combination therapy, and we wanted to sort of expand that to look at sort of key subgroups, including patients that had high-volume disease, as well as patients that were treated with enzalutamide as their ARPI. As we move into early and early and some triplet lines as well, we want to make sure that we are serving everybody with these new therapies.
Tanya Dorff: Exactly. So how did you define your population of those who are more frail? What sorts of measures?
Martin Schoen: We have what's called the Veteran Affairs Frailty Index, which is a accumulation of deficits method that looks across not just comorbidities, but also things like mobility as well as other measures of fatigue and physiologic function. And that because we are not just a medical provider but also an insurer, we can look at things like use of a wheelchair or other products such as diapers or other symptoms that patients can have. And so in this frailty index, we can see who has a higher level of frailty or that is not frail.
We also looked at a more traditional measure called the Charlson Comorbidity Index of greater than three points, and then included patients who had age of 75 or greater.
Tanya Dorff: Okay. So we're looking at elderly, frail and comorbid. The VA also developed something, I think, on number of medications-
Martin Schoen: Yes.
Tanya Dorff: ... also sort of being a benchmark, which I think is really interesting some of these more easy-to-use tools that are really helpful.
But so in your analysis, what did you find? Did the AR pathway inhibitors benefit men across these different groups?
Martin Schoen: Yes, definitely. Actually across all three groups and across as a total. So in each individual subgroup did have a overall survival benefit with the combination therapy, as well as other markers such as time to PSA progression as well as time to next treatment. So both our surrogate markers and our key overall survival showed a benefit of the combination therapy.
Tanya Dorff: So that's great. So there were no groups that dropped out as maybe patients who would be more appropriate for monotherapy? Because there is still monotherapy out there.
Martin Schoen: Definitely. Well, that was one of the focuses that we had with this study is that we had a high volume group, which showed a benefit of therapy.
I would say in the lower volume group, we were slightly underpowered to determine a benefit. And so in patients that were in low volume, there was a, say, modest benefit that met the statistical significance of 0.05, but it was smaller.
Patients with high volume disease did have a important benefit with the combination therapy.
Tanya Dorff: And are you able to also look at toxicities in this analysis and whether there were higher rates of falls or other sort of major events for these patients?
Martin Schoen: Well, in this analysis, we didn't focus on that as much.
In other analysis, we have compared the two ARPIs that have the greatest use in the VA. So abiraterone has been used in about 70% of patients, and then another 25 to 30% have been used enzalutamide. And when we look at things like hospitalizations and the causes of hospitalizations, we haven't found differences in things like falls.
We have had higher rates of cardiovascular adverse outcomes with abiraterone, as well as infections and higher rates of acute kidney injury in patients receiving abiraterone compared to enzalutamide.
Tanya Dorff: That's so interesting. So I guess it's good that we have choices, and we can try to tailor our selection of intensified therapy to our newly diagnosed patient with metastatic hormone-sensitive prostate cancer.
Thanks so much for sharing your work.
Martin Schoen: Yes. No, it's honored to be here. Thank you, Dr. Dorff, for inviting me.