Alicia Morgans: Hi, my name is Alicia Morgans and I'm a GU medical oncologist and associate professor of medicine at Northwestern University in Chicago in the US. I'm so excited to have here with me today, a good friend and colleague, Dr. Stephen Freedland, who is a professor of urology and the director of the Center for Integrated Research in Cancer and Lifestyle at Cedars-Sinai, as well as being a staff physician at the Durham VA. Thank you so much for being here with me today, Steve.

Stephen Freedland: Thanks for having me, Alicia.

Alicia Morgans: Wonderful. So, I wanted to talk with you a little bit about a poster that you and the team presented at ASCO 2021, really investigating metastatic and castration-sensitive prostate cancer treatment patterns using a Medicare dataset. Looking at things like disparities, especially to help us understand how we're using these drugs in real practice. Can you tell us a little bit about the study?

Stephen Freedland: Yeah, so we know from recent data going back to CHAARTED in 2015. And LATITUDE and STAMPEDE, and now TITAN and ENZAMET and ARCHES, that adding something beyond just ADT for metastatic castrate sensitive prostate cancer improves overall survival.

And so, the question is how broadly is this being taken up in the community, one. And then two, are there differences by race and uptake of these therapies? So to do this, we used a Medicare claims database, which went back to 2009 to get the sense of the lay of the land. Obviously that predates CHAARTED and any of those earlier studies.

But then we went up to the end of 2018, which is still a couple of years old, but it's the modern era. Certainly, we had CHAARTED and LATITUDE and STAMPEDE at that point. And so, what we saw is looking over 35,000 patients, a large number. Nice Medicare, you can get large number of patients. Obviously, ADT alone dominated in the earlier years, as you would expect.

But even as we got into the more recent era, even in 2018, ADT or ADT+ first-generation nonsteroidal, anti-androgens, typically Apalutamide, really dominated. In less than one out of four patients got what we would call, intensified therapy with either abiraterone, which was the only one really approved during that time. Or docetaxel.

And so 75% of patients were still getting old line therapies, if you want, which is a little bit disconcerting. But what I would say was more concerting was, when we looked for racial differences, we actually saw that black men were 40% less likely to get one of these intensified therapies.

Alicia Morgans: So, we talked a little bit before we started recording and discussed the real utility of real-world data, and what it can tell us and what it can't tell us. So, can you describe a little bit about what this data is able to tell us about why that disparity may exist or how it's happening?

Stephen Freedland: That's the limitations, I would say, of the real world data is, I think it's wonderful at telling us what is happening, what's going on. It really, doesn't give us the insights that we want into the why. And that's the challenges, is understanding why there's low uptake of these therapies in general. And why it's even lower among black men.

I mean, we can sit here and we had a nice discussion before we started about possible reasons. Is it provider? Is it toxicity? Is it financial cost? Is it of just seeing providers who aren't as aware of these therapies? I mean, there's a lot of potential reasons for this. And ultimately, the real world data doesn't give us that insight into exactly why.

Alicia Morgans: Yeah, I think that's important to emphasize because it really does set the stage for us looking further into this topic in data sets, that might give us a little more insight into what those variables are and how they're playing a role.

But at this point, this is another really massive dataset that suggests that there's overall under-utilization of treatment intensification. And certainly, that it is not an under-utilization that's applied evenly. That really there is a disparity there.

So, how do you interpret what this data means in terms of next steps, both in terms of research and further investigation, and in terms of clinical practice and what we as a field need to do?

Stephen Freedland: Yeah, no, it's a great question. And so, I mean, I think one of the questions is the data go up to 2018, which seems like ancient history. It's only two years ago, two and a half years ago. So, the question is with the ENZAMET coming out and ARCHES and TITAN, has this shifted? Are our numbers improving? I would like to think they're improving.

To what degree are we starting to see resolution of some of these racial differences? Hopefully, yes. But I think also, understanding what are the barriers. And we still see patients coming to us. I'd like to think at our practice, most men will get intensified therapy. If they're very old, very frail, unclear that they're going to live long enough to benefit, but most men should. But we're still seeing in our practices, they aren't.

So I think, getting in and really understanding the barriers as to what's driving some of this low utilization, to me is one of the key next steps. And then what educational needs do we have to overcome these barriers?

Alicia Morgans: Well, this is phenomenal work. Thank you so much to you and to your co-authors. I do know that this was a collaboration with Astellas and Pfizer. I just wanted to make sure that that was mentioned. Did you want to mention that?

Stephen Freedland: Yeah, no, I think that's important is not to negate from the work because I think it's important work. But it was supported by Astellas and Pfizer. And all the coauthors are either employees of one of those companies or our consultants of those companies.

Alicia Morgans: So, thank you so much for explaining all of this to us, I think that yours is not the only study that suggests that there's under-utilization. And I do hope that we see that in data sets, as they mature in terms of Medicare, when we're getting more recent data, that we do see that things are improving.

But I want to emphasize to everyone watching that, the reason that this work is so important is that these intensification strategies are really based, not on how low the PSA goes with your initial ADT. They're not based on patient and clinician preferences. The recommendation is really based on hard data that shows that there's improvement in survival, but also improvement in quality of life for a lot of these approaches.

So, thank you so much for emphasizing this in your work and helping us understand and reflect back to the community what we're actually doing. Because if we don't understand that there's a discrepancy here and actually a disparity between races of our patients, we can't actually take those steps needed to make a difference as we move forward. So, what would your overarching message or summary be to listeners who are trying to understand this data?

Stephen Freedland: Yeah, what I would say is, at least as of circa 2018, there's gaps. There's a difference between the evidence out there, which as you say, is relatively clear. That adding these medications upfront, not only for those who don't respond well or don't get the PSA nadir who progress. That adding them upfront from the get-go improves survival.

There's a gap between that knowledge and what's actually happening in the community. And we need to do a better job of educating the community. And as well as particularly understanding why this is particularly so among black men, which is very concerning.

Alicia Morgans: Absolutely. Well, thank you so much to you and your team for doing this work and for sharing your thoughts about it with us today. Thank you so much for your time, Dr. Freedland.

Stephen Freedland: No, thanks for having me.