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Alicia Morgans: Hi, my name is Alicia Morgans, and I'm a GU Medical Oncologist at Dana-Farber Cancer Institute. I am so excited to have here with me, today, Dr. Pedro Barata, who's an Assistant Professor of Medicine at Tulane in New Orleans. Thank you so much for being here with me today.

Pedro Barata: Thank you, Alicia, for having me.

Alicia Morgans: Wonderful to see you, especially since your recent presentation at GU ASCO 2022 was really informative. Can you tell us a little bit about the two posters that you and the team presented?

Pedro Barata: First of all, thank you for the opportunity to present this study. It was actually quite an interesting effort that we got, that we decided to sit down with our friends from Pfizer and really understand what was going on in the metastatic prostate cancer setting. So, as you know, the landscape has changed tremendously, as far as novel hormonal therapies that are available, and novel agents approved. And I'm talking not only in the CRPC space but also in the hormone-sensitive space. So, what we brought to ASCO GU and presented this year is part of a larger study, where we are really doing that separation of hormone-sensitive and CRPC. And so, what we did is we went and reached out to many dozens of providers, actually, both medical oncologists and urologists from the United States, but also from different countries within Europe.

And we basically captured data on patients they were treating for metastatic hormone-sensitive and then metastatic castration-resistant disease. So at ASCO GU, we presented the US component of that study, and so maybe I'll break it down. So, in the hormone-sensitive space, we had around 50 physicians to help us with that, and from that, we had over 230 patients. And then what we also did is, because we had contemporary data, we limited data around 2020, and we separated to have two periods of time, 2016 to 2018 and then 2019 to 2020. And we were interested in looking at the changes in the management of the disease, knowing that it's actually the period of time where abiraterone became available, and then enzalutamide and apalutamide became available as treatment intensification strategies, in addition to medical castration, for men with hormone-sensitive disease.

So in summary, what we've seen there is actually that the number of patients treated with so-called ADT alone, no treatment intensification, kind of dropped from 40% to about 30% or so. Still a significant number, but it dropped. And then, as expected, we do see the number of patients being offered treatment intensification that was more often abiraterone than the other antiandrogens actually increased, as we get closer to 2020. And so, that was very interesting to see.  At the same time, we saw that the number of patients receiving treatment intensification with docetaxel-based chemo also dropped to single digits, almost, and quite interestingly, too, there are all these patients being offered different treatment intensification regimens that we would not normally consider.

And so, that's the beauty of getting real-world data, I guess because we can get all those patients within the same study, I guess, if you can say that. So, that was basically our report, and I think that is important because it's contemporary, it includes data during COVID, where there were known challenges with axing different medicines. And so, I think it's important, and it's going to provide data for further studies, they're going to leverage what's going on, these days, and how patients are being treated with metastatic hormone-sensitive disease.

Alicia Morgans: I just want to comment that I think it's wonderful that there was an increase in the use of intensified approaches and really, I think, encouraging to see, in a real-world data set, that it is actually occurring. Because we've seen a number of real-world data sets that really demonstrated that there was a disconnect between the data that we know suggests the benefit, in terms of overall survival, quality of life, and other endpoints, but really an under-utilization. So, I think it's really powerful that your study is able to demonstrate that improvement in the increased use of that combination strategy, over time. It's very, very important, I think.

Pedro Barata: Yeah, no, I fully agree. And thank you for that. And one of the things that I found interesting is the fact that we were able to get data from our friends from the urology side, and it's interesting to see how sometimes different their patterns are, compared to medical oncologists. So, for instance, urologists, as expected, would tend to use less chemotherapy-based regimens and more novel hormonal therapies. They tend to use more antiandrogens, a CYP17 inhibitor, for example, than medical oncologists do, and that's interesting, not only in this portion of hormone-sensitive but then in the CRPC space.

Alicia Morgans: Very, very interesting. I love those breakdowns. What did you find in the metastatic CRPC space?

Pedro Barata: Sure. So, we did the same methodology, if you will, so we had, again, a few dozen of physicians to help us collect that data. We had over 130 patients or so included in that, who had metastatic castration-resistant disease at the time of the study analysis. And then, we started by looking back at how they were treated, prior to CRPC, and we still had a significant number of patients, a little bit over a third, who were treated with ADT alone, so no treatment intensification. But we did have a percentage, it was a good percentage, if you will, of patients treated with mainly novel hormonal therapies.

And then, what we saw in the first-line CRPC, in both the urology and the medical oncology setting, is that actually providers are favoring the novel hormonal therapy in that setting. So, even though NHTs, novel hormonal therapies, were common in the hormone-sensitive space, in that patient population, they were still being offered a novel hormonal therapy in the first-line CRPC. And here, the dominant agent used was enzalutamide, which, if we look back, and we see the breakdown, we will see that, in reality, the sequence abiraterone, enzalutamide seems to be a common approach in that scenario.

There's also another aspect that, in this particular setting, we did find a difference in terms of utilization of treatment intensification. Fewer patients were offered treatment intensification when they were managed by urologists versus medical oncologists.  I think this would support the fact that we need to talk to each other and be up to speed with all the new regimens coming up, and it is all very recent. And so, I do think this trend is also going to change, as we talk more and more, and as we saw at ASCO GU, more data from novel combination regimens, like ARASENS, for example, or PEACE-1 we saw recently, too.

So, a few patients are actually being offered a triplet in the hormone-sensitive space, and when they progress, it seems like they are still being offered, commonly, a novel hormonal therapy, a few of them are being offered a subsequent chemotherapy agent. So, there is definitely this sequencing that's been interesting to see. Again, there are obviously factors that we couldn't quite control, and COVID is perhaps one of the most obvious ones, but I think that data provides us some insights into how we're managing patients with metastatic prostate cancer, these days.

Alicia Morgans: Absolutely. Now, one of the things that might not have been captured by your data set, but that I think would be interesting to look at, if you do have the data, is how long that second agent, in the metastatic CRPC setting, actually was used. So, for example, if you had abiraterone in combination, in the metastatic hormone-sensitive setting, with ADT, and you had then switched to enzalutamide for your mCRPC first-line treatment, how long did you stay on that treatment before it either was effective or not effective, and you had to switch off? And you may not have the duration of treatment information that would really answer that question, but I would love to hear your thoughts.

Pedro Barata: Yeah, I know, this is a very, very good point, and you've run multiple real-world studies, yourself, so you know one of the challenges, when we get these kinds of studies, is how do we define what's the real-world endpoint that is similar to, or resembles, where we want from trials, right?

Alicia Morgans: Mm-hmm (affirmative).

Pedro Barata: So, I'm talking about things like radiographic, progression-free survival. We cannot really get that because scans are not happening at the same time, providers call progression differently, and so perhaps time on treatment, as you mentioned, might be one of the surrogates, in the real world, that we could use to infer what's going to happen, in terms of efficacy of that agent. We are actually writing the manuscripts as we speak, so we are trying to look into that. So, this is a very timely point, so thank you for bringing that up.

Alicia Morgans: Wonderful. Well, if you had to summarize this data, which as you said, is actually a subset of this larger study that you and the team did, so I commend you on the entire thing, what would your summary be?

Pedro Barata: Yeah. So, I really think that number one, the changes that we have seen in the last five, seven years have been dramatic, and we are seeing that in daily practice, in the different offices and hospitals, institutions around the world, at least in the US and in Europe. Access to therapies is different and depending on where you actually are and where you actually can treat those patients, it's very different, what happens in the United States versus different countries within the EU. And so, we can actually have an understanding of that when we look at that data when we bring the European data in addition to the US data, if you will.

Saying that I do think that the phase-three trial data that has been presented, in these last several years, with docetaxel, abiraterone, enzalutamide, apalutamide, and other triplets, I think we have started to see a pickup of treatment intensification regimens for these patient populations. And I think what this real-world data is going to show us, as far as outcomes, for example, survival, with longer follow-up, is actually by doing so, we are actually helping patients. And so, the trial data seems to be supported in the real world, and providers that see patients on a daily basis are using trial data to offer that to patients. And that is, I think, I would summarize as good news. We are actually seeing what we want to see which is actually improving outcomes of patients, and patients are getting what has been shown to be successful in the trial setting.

Alicia Morgans: Absolutely. And that is one of the big powers of this kind of approach to analyzing real-world data, to understand what's actually happening in our communities, and what are patients actually receiving? We can do a million trials, but if we aren't actually using the information to guide our daily practice, we're not making a difference where it really needs to be made. So, thank you so much for this investigation, and thank you for those encouraging words about progress in our practices. I really like to hear that, and I appreciate your time and your expertise.

Pedro Barata: Thank you. Thank you for having me. It's always a pleasure to chat with you. Thank you, Alicia.