Melissa Abel: Thanks for having me.
Tanya Dorff: I was very intrigued by your study that looked sort of like a natural history study. You're taking men with biochemically recurrent prostate cancer, which is a very common scenario we see in our clinics, and following them with imaging to see how their disease evolved over time. Tell me a little bit about what made you want to do this study.
Melissa Abel: Yeah. I think the impetus from this study is that men with BCR are a heterogeneous group, but largely can have a good prognosis where it can take many, many years before they develop conventionally metastatic disease, even without therapy. There's obviously some who are in a higher-risk group, but a lot of them are not. Now we have the introduction of PSMA PET scans coming in and we're seeing disease that we used to not be able to see that is metastatic, but isn't metastatic to the same extent that we see with conventional imaging. These are all patients that... We like to refer to them as PSMA-positive BCR, because it retains the history of what we know about BCR, which is where these patients would've fallen in historical trials. These are not patients that would've been eligible for any of our metastatic disease trials because their disease wouldn't have been detectable without PSMA PET.
It came out of a concern of, okay, how should we use these new scans? It's a new disease state that we're identifying. It's always existed, but now we can see it in a different way. And how should this new information drive therapy? A lot of these patients are being treated with mCSPC therapy approaches, even though we know that many of them can live for a very long time without therapy. And so there's a high risk of overtreatment. And so, how can we better define who needs treatment, who can be observed, and should PSMA PET imaging data change that?
Tanya Dorff: Yeah. Well, I certainly hope that many of us are not treating these patients with lifelong doublet or triplet therapy just because we see a couple things on the PSMA PET. I agree with you, it's definitely a different disease state. But tell me about the kinds of treatments that patients were receiving on the study. Was it mandated or was it totally left up to the treating physician?
Melissa Abel: Yeah. These are all patients who have had recurrent disease after definitive therapy, including salvage radiation. These are all patients who've, if they had surgery and then recurred, already had salvage radiation or declined it. And then, while on study they can be off therapy or their intermittent therapies are allowed. Initially, this was pre-EMBARK when it was designed. This was designed so that patients could, if they chose to or if they were particularly high risk at intermittent ADT, it allows for SBRT. Basically, any therapy that lasts less than six months. We also have clinical trials in our group with intermittent ARPI therapies and Radium-223 trial that I presented at this meeting. Those intermittent trials were allowed, but only about a third of patients thus far have gone on therapy. The majority of them are being observed.
Tanya Dorff: Whether they're getting a treatment or not, how frequently are you doing the PSMA PET scans on this protocol?
Melissa Abel: Yeah. The way it works is we get... They have to have at least a PSA of 0.5 to be eligible. And then we get a baseline PET scan. If that PET scan is negative, we get annual imaging. If there's anything on it, even if it's equivocal, we get every six-month imaging.
Tanya Dorff: Great. Tell me a little bit about the group that's probably the most interesting that we lack data on, which is those guys where you see something on the PET scan and then who did not get treatment. Because it sounds like you're saying a lot of the patients in this study did not get treatment.
Melissa Abel: Yeah, correct. And this study's still ongoing. We're currently in a median follow-up of about two years, and we're hoping to get some interim data out soon on the follow-up. But the data I presented at this meeting was the baseline data of the first 130 patients. Just looking at one time point, how does PSMA PET imaging data relate to PSA doubling time, which is our best metric of prediction for metastatic disease in BCR. What we've found is that even patients with very slow PSA doubling times who are felt to be low risk, patients with PSA doubling times greater than nine months, greater than 12 months, the vast majority of those patients do have things on their PSMA PET scan, at least when their PSA level is above five. We see lymph node disease.
We occasionally will see small micrometastasis in the bones. Small lesions in the bones that are concerning, but of unclear if they're cancer or not, but things that are concerning and questionable that we need to better understand. And disease that's also recurrent in the prostate bed. Especially these slow-doubling-time patients who are lower risk. And even we have patients with faster doubling times as well who are being observed off of therapy because they don't have a lot on their scans. There's not an immediate threat and they're like, "Yeah, let's wait another six months and see what the scan shows before we pull the trigger on therapy." And so, we just keep going. And if things aren't really changing on the scans, we observe them. We're hoping to really gather a lot of data of how this disease data evolves and how we can use it to better risk stratify patients.
Tanya Dorff: But it sounds like, at least so far, I know you're mostly presenting baseline data, you don't have as much on the follow-ups. But it sounds like you're not seeing like, oh, my goodness, people's disease is exploding-
Melissa Abel: Correct.
Tanya Dorff: ... in that six month interval and we need to shut this down and mandate treatment for everyone.
Melissa Abel: Yeah. Yeah. No, my colleague, Ravi Madan, had a poster that showed... It was a smaller subset, or about a one and a half year follow-up, how many patients had progression on conventional imaging. And now I think out of the first 150 or so, that number's five. It's a minority of patients. And that includes a lot of our patients who end up with really fast doubling times and changes happening on their PET scans, we do start on therapy, EMBARK therapy or intermittent ADT. That includes patients who were treated and then still progressed. There are a small subset of patients that do have this more aggressive disease, but over 95% of them have not had drastic sudden changes on their PET scan that really differed from what their PSA or their PSA doubling time is doing. But still early, so we're working on analyzing that follow-up data now.
Tanya Dorff: Hopefully you'll be able to give us some insights from this population, which is a really unique cohort and dataset. We're looking at options now from SBRT alone to these oligomets, SBRT with some kind of ADT or just ADT doublet, or even ARPI monotherapy. The number of choices is expanding. Do you think this dataset will give us some insights into which patients might be best served by which option? And I left off the option, of course, of observation, which maybe will come onto the table if we see continued reassuring data from your study.
Melissa Abel: Yeah. No, I hope so. Obviously, there's a subset of BCR patients who will benefit from therapy, there's no question. But there's also the majority of them who do have more indolent behaving disease that are at high risk of being overtreated as well. My hope is that we can better just use this data to better decide who can be observed off of therapy, even if it's just for a certain amount of time. How can we create better guidelines as to, it's okay to watch and then maybe this is the trigger for when... The same way we do with active surveillance for Gleason 6 prostate cancer, close monitoring, but observing off of therapy for a period of time for these patients, even when they have things that we can see on their PSMA PET scan.
Tanya Dorff: Fantastic. Thank you so much. I look forward to hearing more about the study in the years to come.
Melissa Abel: Great. Thank you.