The Growing Field of Radioligand Therapy and Radium Use for mHSPC and mCRPC

David Morris, MD, FACS; John Phillips, MD; Jeremy McDuffie, MD; Katy Beckermann, MD, PhD; and Alan Tan, MD, discuss the evolving role of radioligand therapy (RLT) and radium-223 in managing metastatic hormone-sensitive and castration-resistant prostate cancer in part four of their roundtable discussion. The group explores the shift in radium use from a last-resort option to an earlier intervention, the challenges posed by emerging therapies like lutetium, and the increasing accessibility of RLT in clinical practice. Dr. Phillips highlights the promise of radioligand advancements, the growing enthusiasm within radiation oncology, and the potential impact of trials like PEACE-3 in redefining treatment timing and patient outcomes.

Watch the fifth part of this series: Upcoming Trials for mHSPC and mCRPC and Next-Generation Sequencing

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Dr. Morris:
So I’m going to get to you in a second as adding in finally RLT therapy, I mean obviously this is a very growing field for radiation oncology and all of us because all managing and referring, but if anybody can make a comment on there’s this kind of a sister trial to ARANOTE, the ARASEC trial being run here in the US that is unique in its design.

And I don’t know if your sites are participating, our community site was participating, but it’s basically to try to get some American data from US patients, a little bit different genetic makeup of some of the Asian and ex-US populations looking at darolutamide combination ADT versus a charted historical control. So not looking at any active live patients getting just ADT, but looking at matched historical control. So I think there’s a lot of anticipation that it will read out and show versus a charted placebo patient that a doublet will once again be coming back to the forefront for discussion that we should always be doing doublets when almost never be doing monotherapy.

But I think the claims data unfortunately shows us otherwise that we’re not doing that even in community where we’d love to have a simple, it doesn’t matter what disease state, it doesn’t matter triplet or doublet, it doesn’t matter volume, I just use this with ADT, they’re automatically paired. So hopefully we’ll get more information and maybe be able to access that more easily and not necessarily off-label.

But John, just in terms of adding in radium early in the process for metastatic because explain kind of our use now for radium and metastatic CRPC, how is it different than what this P draw was looking at?

Dr. Phillips:
Yeah, radium historically has owned this space of a last resort, right? It is the therapy we give to guys who have diffuse bony metastatic disease and have been through every other line that we have. And if you look at the radium trials, what I always counsel patients on is, “We don’t expect your PSA to change, but you’re going to have less skeletal events. You’re going to have a slightly longer survival.”

And I think moving radium up the chain is a big sea change for radium and I think it’s challenging as Jeremy said, to figure out who is the right patient to move into that space. And we’re still reacting because there’s so much change happening in radioligand therapy right now. We’re all waiting to see if lutetium gets moved up ahead of Taxol, even though if the FDA will prove it because there’s some concern that maybe that trial’s comparison arm doesn’t really validate it very well.

And so I think the biggest takeaway I have about radioligand therapy right now is it’s going to be different in six months, 18 months, three years than it is right now. And it’s going to change pretty rapidly. There’s new agents but there’s also new indications coming. So I think as Jeremy said, we’re still in the very early figuring out who to move upstream with radium, especially in the era where patients come in with their lutetium Pluvicto pamphlet and they’re like, “This is what I want.” And so we’re still-

Dr. Morris:
Don’t feel special. They show up for their biopsy asking if they’re a candidate. So we ask for PSMAs before we’ve done a biopsy. So there’s a lot of things that direct to consumer lead to a lot of confusion. I think that’s another example of it perfectly.

Dr. Phillips:
Yeah, I think from a radiation oncologist perspective, we have external radiation and we have some newer developing technologies around proton therapy. But if there’s one therapy in our field that I’m most excited about, it’s the direction we’re going with radioligand therapy. I chair ASTRO’s White Paper committee on safety and quality of starting a radioligand program. And it is basically like cheerleading, it’s trying to get people out of the basement and into the clinic to give these therapies because they’re not particularly challenging to give.

The toxicities are relatively manageable and once you kind of figure out a safety and a plan for handling the materials and all of those things, they’re relatively easy additions to your clinic.

And so I think we’re going to see this rapid growth in RLTs over the next few years. And so where things fit into play right now is going to be different even by the end of 2025, but by the end of 2030 they’re going to be everywhere.

Dr. Morris:
So as I currently manage patients progressive with bony disease and symptoms, clearly what the label for radium is now, I’m often having to wait almost longer than I would want for a therapy. So I’m hoping, and I’d like your thoughts on do you think the PEACE-3 would change where I could have somebody early in the disease transition where I could say I’m sending them based off this data, there’s still going to be benefit as opposed to me waiting for symptomatology?

Dr. Phillips:
Yeah, I think we’ve always been a little dissatisfied with having to use it so late. And the reason is because they’ve been exposed to so many lines of therapy at that point. Radium does carry some bone marrow toxicity, and so every time we give an infusion, we check their blood counts and a lot of these guys bottom out before their end of their course. And so being able to move it upstream means guys are going to be more likely to complete the entire course. They’re not going to have this intense toxicity, have to skip cycles or stop altogether due to anemia or low platelets, things like that.