Comparing Alpha and Beta Emitters, and Looking to the Future of Advanced Prostate Cancer Care

David Morris, MD, FACS; John Phillips, MD; Jeremy McDuffie, MD; Katy Beckermann, MD, PhD; and Alan Tan, MD, explore the distinct roles of alpha and beta emitters in radiopharmaceutical therapy, the promise of triplet therapy, and the integration of precision medicine in the final segment of this roundtable series. They discuss the operational challenges and clinical considerations of radioligand therapies like lutetium-177 PSMA and radium, their impact on patient outcomes, and the potential to move these therapies earlier in the treatment paradigm.

Watch this roundtable series from the beginning: Biomarkers and Imaging in Upfront Metastatic Prostate Cancer Diagnosis

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Dr. Morris:

So could you touch, I mean as a radonc, you can get in the weeds on this, but can you touch a little bit on the differences between an alpha and a beta emitter in terms of… You mentioned operations being a challenge for this, and I would say as somebody who’s tried to build a radioligand treatment center and currently gives it in the office and the community, it is a challenge. So can you speak a little bit about the differences between the two and why they’re not all created equal.

Dr. Phillips:
In the easiest to terms alpha emitters give their radiation over a very small distance. Beta emitters can give it radiation over a larger distance. It introduces some challenges and how you store things and the exposure, they’re both excreted very differently.

So one of the biggest challenges with Pluvicto is patients that are incontinent. And so we have to be very, very cautious about how we screen patients who are going to get Pluvicto because if they’ve had an RP previously, if they didn’t come in metastatic but had definitive therapy and they’re using six pads a day, we’ve shared patients where we’ve tried doing clamps and it’s just a tremendous challenge to get those patients through. Whereas radium is primarily excreted through stool, and so you have to kind of think about that as a very different therapy.

I think that there are other challenges where we’ll give radium through a port because it emits things over a much smaller distance, but Pluvicto can cause port burns if you give it through port. And so each one, and I think we’re eventually going to have alpha emitters that are PSMA conjugates. So they both have different pros and cons, but they’re very different in how you handle them, how you administer them, and the patients that can do radium even though they’re incontinent but can’t do Pluvicto. And so it’s kind of a myriad of considerations.

Dr. Morris:
And any special toxicity that you’re more concerned about between the two. We see more radium patients than we see lutetium patients usually that’s deeper in the therapy lines, but anything specific that we call out that we need to be looking on the front end before I even refer them over.

Dr. Phillips:
The big thing for both is just the hematologic toxicity. So whenever you’re given these therapies, you just have to be extremely mindful of their hematologic toxicity. We schedule all of their lab draws the day one, so when they get their first of their order sets, it comes with all of their subsequent lab draws.

I think with radium and some of the combinations with ARSi, we worry about skeletal events, more fractures, things like that that can show up. And so they’re different, but they’re more similar than they are different with the main concern being hemostat.

Dr. Morris:
Well, I think we’ve about reached the end of our conversation piece, but I’d love just your one takeaway for what is it that you’re excited about? What is it the one thing that with advanced prostate cancer, whether it’s de novo, whether it’s progressive, that you feel that you’re coming back to, “I need to get testing,” or whatever it is, what’s kind of your main thing that you feel like we need to be paying attention to as a field for advanced prostate cancer?

Dr. Phillips:
I think I’ve said mine already, which is that the landscape for radiopharmaceutical therapy is going to change dramatically over the next three to five years. The amount of investment that’s happening in that space is astronomical and the indications are going to keep moving upstream in the chain of treatment. And so we may be having this conversation in two years talking about do we give people RPTs as primary definitive therapy. And that’s the nature of how all therapies move from the metastatic end stage space upstream.

And so I think we’re at the very start of that and in a few years we’re going to be saying like, “Oh, is this a good patient for RP and Pluvicto?” Like we’re going to be talking on those terms. And so I think it’s just an exciting development. If there’s one thing I’m excited about in radiation oncology right now, it’s the transition to radiopharmaceutical therapy.

Dr. Morris:
Jeremy, in the community, what do you come back to?

Dr. McDuffie:
I think I’m most excited about when you look at the triplet therapy regimens, the amount of people that get PSA undetectable disease, the reason that that’s exciting is one, patients are happy when they’re undetectable. But two, I think that allows eventually downstream was being said by my radiation oncology colleague that then other things can be brought in. If it’s know oligometastatic progression, the ability to potentially give treatment. Holidays allow patients to have a much better quality of life downstream of that undetectable PSA. So I think as somebody managing these patients, the potential to really give them enhanced quality of life downstream is kind of what we’re causing.

Dr. Beckermann:
Yeah, I feel like prostate cancer is becoming a more personalized treatment. Cancer, we’ve always had PSA, but I think between PSMA PET, between now genetic testing, we’re kind of being able to say, we’re going in and we’re making these thoughtful decisions about what to do next, and I look forward to seeing that develop going forward.

Dr. Morris:
Alan, what’s your last take?

Dr. Tan:
My last take made be common, long, but we have now lutetium PSMA, we didn’t talk about moving that up into the frontline setting. We actually fully accrued PSMA addition now, and we await for that readout. But I think it’s exciting to think about a new triplet one that’s not chemotherapy, one probably going to be well tolerated, I would say, and then it really changes the landscape, makes it more complicated. Again, where does chemo fit after that.

Regarding PEACE-3, I think we should also touch base on this is a radioligand that’s highly effective. The hazard ratio for RPFS was 0.69. The hazard ratio for overall survival was exactly the same. So this is still a very highly active regimen. Of course, the population is different from our contemporary population, but let’s say half of these patients are on single agent ADT in the rural communities. Those are the populations that could probably fit into enzalutamide plus Radium-223 in first line CRPC.

And then, yeah, then precision medicine up the wazoo. I mean T-cell engagers. I think the chance to actually have a durable remission, a chance for even a cure with cell therapy is sounds really exciting to me.

Dr. Morris:
Yeah. Well, I’d like to thank everybody for joining us for this GU Oncology Now update roundtable about prostate cancer. Thank you. And thank you for your attention.