Dustin Boothe: Yeah. It's something that you have to disclose and discuss at length. And we have three levels of communication within my practice. First, it's me going through everything, the need to have access to a bathroom that only they use, sleeping separately, distance between them and close ones, that there's the time period between everybody, and then also pregnant women and children. It's interesting, I run a trial for patients, a radiopharmaceutical trial for breast cancer patients, and I run into this a lot more just because the population of mCRPC in general, it's older men that probably don't have young ones at home, and probably most times are able to keep those restrictions.
When I was in Colorado previously, I did a lot of radioactive iodine, and Phil, I ran into that problem more so. I don't come across it as much as I feel like I anticipated when I start my program, I think it's because of the patient population. But we go over it again and again, and sometimes I think the challenges that I run into is educating family members, making sure that our patients are not being banished to their rooms. That you can be very safe and still eat at the opposite ends of the dinner table, and you can still go on walks around your house, and you don't need to be locked in your room for three days, but you need to follow the basic precautions, and I feel like most times we're able to make that happen.
Sometimes we need to send some grandkids that live with their grandparents to another family member's home for a period of time. But fortunately, I feel like because this patient population, we're able to deliver it safely. But as this moves up in line and extends disease sites, these are going to be issues that are going to be more and more important that every practice communicates very effectively and very clear on how to keep family members safe.
Phillip Koo: Yeah, I agree. Lots of misinformation, but in the end, I think it's a lot easier than what we experienced with I-131. So, Dustin, I'm going to reverse the order now. So, what is one of the biggest gap that you see with radiopharmaceuticals, and how we might close that gap? So, I'll start with you and then I'll go the other way around.
Dustin Boothe: My desire is to get this effective medicine and this effective paradigm in as many situations that make sense and in the most effective way possible. I think the gaps that I struggle with as I prescribe these medicines is I want to be equipped with the tools to select patients better. Those studies were good that led to the approval of Pluvicto, the studies are good that have supported the use of Radium, but I want more biomarkers. The PET scan is helpful, but I think there's more to the story. And I think we can see improved deltas on these Kaplan-Meier curves as we get better at selecting patients, both whether these radiographic or clinical or other biomarkers to help us select them. I feel like that's a big gap. The other is, I think in the hormone-sensitive setting, I'm excited about the PSMAAddition data, it's early.
I want to see that this therapy is being used when it's most effective, and that is when there is PSMA avidity, and that there's expression of these tumors. I worry a little bit about the way these studies have been designed in a way to give them at a point that maybe the PSMA expression has been muted. And so, I think we need to optimize PSMA expression in collaboration with delivering these therapies, in addition to the biomarkers. I also love the work that Jeremie Calais and Louise Emmett's doing in terms of adaptive strategies, those data are going to be really fascinating, and I hopefully think will be practice-changing so we can really make this decision precise and individual, not just based on upfront, but also on how they respond.
So, those are a couple of things, but there's so much and smarter people than me on the call who can continue to opine here, but those are some things that I still have left some room for wanting here.
Phillip Koo: Great. So, Neal, from a urologic oncologist perspective, what are some of maybe the biggest clinical gap that you see?
Neal Shore: Well, just from a practical standpoint, we still have a tremendous amount of variability in how the reports are performed. And there's even a lot of inter-observer assessment, whether it's you're using SUV mean, or max, or total SUV volume. And so, the reports, there's not any true harmonization. And I think we've gone from zero to 60 a little bit too quickly on that. And there's probably going to be different, and should be, different metrics for resistant versus sensitive biology as we think about prostate cancer patients. And I absolutely would echo the concept that, how do we better think about not only where there is avidity, but other biomarkers as well and other specific clinical presentations? Because we want to be more precise in how we think about how we employ this really active therapy. And then also a big unmet need or a gap would be how do we really ideally combine?
PSMAAddition was designed with an RP, I'm actually kind of excited about some trials where we're looking at delaying testosterone suppression, and even in the BCR population. So, there's real opportunities, particularly not only in the reporting and the harmonization of that, but also in some of the other opportunities for the radiopharmaceuticals that could be combined and also avoid testosterone suppression.
Phillip Koo: So, Tanya, I'll give you the final word here.
Tanya Dorff: Yeah. So, the others have touched on two really important areas, right? Selection and then dosing. And dosing could be intensification, could be de-intensification, can be combination. But I think one other gap is monitoring, I think people don't really know how to follow patients. We know PSA can go up before it goes down with that first dose, doesn't mean it's not working, but we also know PSA declines are associated with benefit. We don't know what the PET scan should look like after two or three or four doses.
So, I think a little more work in there is going to help clinicians optimize their application. And then also the radiobiology, the science, why do two different patients with the same kind of PET scan avidity respond differently? There's something different about the actual tumor biology. So, I think we need to continue to do the science, that's really going to drive the breakthroughs in terms of both selection and dosing and combination strategies.
Phillip Koo: Wonderful comments, I think we all agree, radiopharmaceuticals, this is the early part of the journey, and a lot more to come, and great scientists like all of you will hopefully help answer those questions. So, thank you so much for sharing your expertise and we really appreciate it.
Tanya Dorff: Thanks.
Dustin Boothe: Thank you. Thanks for having me.
Neal Shore: Thank you.