Zachary Klaassen: Hi. My name is Zach Klaassen, urologic oncologist at the Georgia Cancer Center. We are in Chicago 2025 ASCO Annual Meeting. I'm delighted to be joined, as always, by Dr. Steven Finkelstein, radiation oncologist in Syracuse, New York. Steven, thanks so much for joining us on today.

Steven Finkelstein: Thank you so much for having me.

Zachary Klaassen: We've seen a lot in the last two months with radioligand therapy. And we've seen Pluvicto, obviously approved several years ago with VISION now pre-chemo post-ARPI. Just take us through the excitement around ASCO and that journey that got us to this most recent indication.

Steven Finkelstein: Yeah. It's really amazing to see the enthusiasm at ASCO for radiopharmaceuticals. Even getting off the airplane, walking through O'Hare, you see things about people talking about radiopharmaceuticals in a way that we have really never seen before.

Zachary Klaassen: Yeah.

Steven Finkelstein: How did we get here? So building on the building blocks of radiopharmaceuticals in alpha emitters with radium-223, which was incredible work to help our patients. Now, for the first time, we have a therapeutic beta emitter that is a theranostic.

That theranostic was approved based on the VISION trial, which looked at patients who had PSMA-positive disease, and we'd be able to treat it with a therapeutic beta emitter which would actually go after that specific protein on prostate cancer cells. But we could not give that agent after VISION to patients who had not seen chemotherapy, and that was probably to patients' detriment.

So, a trial was done by that group, Novartis, to look at that space. And that was PSMAfore. And PSMAfore demonstrated a 59% reduction in its primary endpoint, looking at relevant cancer outcomes in patients now in the pre-chemotherapy space. That was, I think, a huge blow for freedom.

Zachary Klaassen: Yeah.

Steven Finkelstein: And when we think about this, we finally had the ability, after seeing the data from this trial, to potentially offer that to patients. And as you know, only a few months ago, the FDA approved Pluvicto in the pre-chemotherapy space for patients who have PSMA-positive disease and had basically failed in ARPI. This, we think, is so exciting as we think about the ability to help patients with radiopharmaceuticals.

Zachary Klaassen: And I think too, I mean, we've talked about this on UroToday, the denominator has gotten so much bigger as well. So we look at now FDA approval end of March 2025. NCCN just two weeks later, has an update that has Pluvicto now as an option in that pre-chemotherapy space. Just talk about how that's changed your clinical practice even in just two months.

Steven Finkelstein: Yeah. I think it's really enlightening to see people sometimes are waiting for long periods of time for NCCN approval for agents. But we had the data come out for PSMAfore. We had the FDA approve Pluvicto in the pre-chemotherapy space. And I was able, as you know, to give the first dose to a patient in the pre-chemotherapy space on label within six days.

Zachary Klaassen: Yeah.

Steven Finkelstein: And then shortly thereafter, two weeks later, after that the NCCN approved in this space showing, I think, the enthusiasm we have to help patients with this area. How is that going to transpire? Well, I think that it will probably triple the amount of patients who can see radiopharmaceuticals like Pluvicto in this space, amounting really to a tidal wave of enthusiasm to help patients with radiopharmaceuticals.

Zachary Klaassen: And I think too, we talked a little bit off camera about the tolerability. Just talk a little bit about that. Now that we're able to move it up just a little bit in that pre chemo space, just talk about tolerability.

Steven Finkelstein: Yeah, speaking as a radiation oncologist, we're always concerned about balancing the treatment efficacy and the side effects. And the side effect profile of Pluvicto has been, I think, extremely favorable. One of the things that I think is interesting is we delve deeper into it is that for me, there was an interesting piece about for hematologic side effects being lymphopenia.

Now, Neal Shore and I had published about 10 years ago about the importance of ALC. And we said that ALC drops with cancer therapy. But it was not a significant enough drop as you could harvest cellular-based therapies. And what I'm really talking about is being able to give Provenge.

Zachary Klaassen: Sure.

Steven Finkelstein: But I think now as we get deeper into this, there is a deeper understanding of how important the immune system plays into how these therapies are actually working. Our work with Patrick Sung, I think, is really trying to continue to enlighten about how important the immune system is in this. And I think we're going to see how this interplay between the immune and radiopharmaceuticals happen and ways to mitigate that.

So I'm excited about the fact that the side effect profile from this was very favorable. But I'm also thinking about how we can even get better.

Zachary Klaassen: Yeah. What are your thoughts on that? Let's just dovetail into that, how can we get better?

Steven Finkelstein: Well, I think that the answer is to understand the mechanisms as we understand the mechanisms of how our therapies work. As a radiation oncologist, I think about this as, this isn't a drug, this is a radiation agent. And it has unique nuances. We spend our lives as radiation oncologists learning about how radiation interplays with patients to get better cancer outcomes.

We, I think, love to work in a multidisciplinary role with nice gentlemen like yourself in urology. In my work with Chris Pieczonka, who's an incredible urologist in my group, AMP, in Syracuse in the US Urology Partners Network. I think it's so important to work together to basically try to learn some of these things. Our interactions with industry are really going to help. I think the work that groups like Patrick Sung's group are doing to move that bar forward are going to be insightful for our future.

Zachary Klaassen: Yeah. Two great buzzwords from today-- so multidisciplinary and excitement. Any closing remarks in terms of this discussion looking at the NCCN updates? I think this has been a great couple of months. It's going to be a fun end to 2025. Some several statements to conclude.

Steven Finkelstein: I think being here at ASCO, it is amazing to me and exciting to me to see the tidal wave that is radiopharm. But I'm-- five years from now, I am so excited where I think we will be building upon the building blocks of our past. So again, absolutely a pleasure being here at ASCO. Always great to be with you, and I'm excited about our future.

Zachary Klaassen: Thanks so much, Steve. Great discussion as always.

Steven Finkelstein: Thank you sir.