Read the Full Video Transcript

Alicia Morgans: Hi. I'm so excited to be here today with Dr. Rana McKay, who's joining me from UCSD to discuss her poster at GU ASCO 2025 on radium. This was a systematic review. Thank you so much for being here today with me, Dr. McKay.

Rana Mckay: Of course. Thanks so much for having me.

Alicia Morgans: Wonderful. So Rana, tell us a little bit about what you did, why it was important, and why this kind of work is really necessary.

Rana Mckay: Now, this is really important work. Radium-223 was approved in 2013 at a time when the treatment landscape and mCRPC was very different than what it is now. It was actually not even the time where we were kind of systematically using RPs in this setting. They were just getting approved, thinking about radioligand therapy, PARP inhibitors—this was well before that time.

So really, this review focused on the real-world outcomes that have taken place over the past decade, since the treatment landscape has just so dramatically changed. The systematic review is the most comprehensive that's ever been conducted for radium-223. It included 48 studies, over 15,000 men with mCRPC that have been treated with radium. Over 1,000 different citations.

So really kind of trying to be as comprehensive of all the modern-day data. And it was everything really encompassing the last decade from 2014 to 2024. It included European studies, American studies, North American studies—so 22 European, 18 North American studies. And the sample size of the studies that were included ranged from as small as just 100 patients to 1,600 patients that were involved.

The median age of the patients that were kind of reflective in this population was around 65 to 76 years old. About 50% of patients that were included had received prior chemotherapy. 50% had a prior RP. And so that was kind of the population of men that was analyzed in this systematic review.

Most of the studies reported out that about 55% to 64% of patients had actually completed five or more cycles of radium. As we know, radium is given IV every four weeks for up to six doses of treatment. And we looked at actually treatment utilization of radium-223 and what were the factors that predicted for somebody actually being able to complete the intended therapeutic course—either five or six doses of the radium. And earlier line of treatment, no prior chemotherapy, stabilized hemoglobin, and neutrophil counts, as we would kind of all expect, seemed to be factors that were associated with actually being able to complete the therapy.

With regards to the efficacy outcomes, we did look at median real-world overall survival in the context of this analysis. And it was really variable—ranged from anywhere from nine months to 23 and a half months. Nearly a third of the studies reported median survival of 15 months or greater. And there was definitely an association with patients actually being able to complete all five or six cycles of radium with median overall survival, and we saw a two- to five-fold increase in median OS in people that were actually able to complete all cycles of radium.

The progression-free survival—obviously, in the original ALSYMPCA study this was not reported, and I think the PFS data has been variable for radium-223, but from what is reported in the literature, it ranged from 4.3 to 7.3 months. And across the board in studies that reported on pain outcomes, we saw reduction in pain. We saw reductions in ALK phos—not every study reported on PSA outcomes, but in about 20% of individuals where there was reporting on PSA outcomes, we saw actually PSA reductions.

So we did look at the safety profile as well. And one of the big things with radium-223 has been the fracture risk. And really, across the board, the fracture incidence was quite low—less than 10%. But of the 43 studies, I think there were 12 to 14 that actually reported on fracture rates, and the rates of fracture were much lower in people that were actually on a bone-protecting agent.

So I think overall, kind of in summary, this was the most comprehensive systematic review of modern-day receipt of radium and how it's currently being utilized in the current treatment landscape. And radium-223 is a life-prolonging agent for mCRPC. And data has demonstrated that mCRPC is a tremendously undertreated disease. About 25% of patients never actually see any therapy for mCRPC. And of people that receive one line of treatment, at each iterative line, there's a 50% drop-off in people actually being able to see a second line or a third line. And when we look at real-world overall survival data for people that have mCRPC, the real-world OS is around two years, which is very different than what we see in clinical trials.

So I think when I have a patient before me, I'm constantly thinking, how can I make sure that this individual has access to and realizes the benefit of every life-prolonging therapy that they have available to them? So I think that this data is really instructive about where we've come from the original ALSYMPCA study.

Alicia Morgans: Wonderful. And I so appreciate that this study is really able to help contextualize the use of radium in a modern era where we have so many different treatments available that certainly were not even considered possibilities as the ALSYMPCA trial first led to this drug's approval.

One of the things that I thought was really interesting in PEACE III is that this study, obviously looking at radium with a combination of enzalutamide in that first-line mCRPC setting, included patients who were asymptomatic or minimally symptomatic. And when I think about radium in practice, I know the label has had some dramatic kind of tied into that, and I envision that actually in a pretty broad way. This patient may have some mild fatigue or may have some other issue, but I don't necessarily think in my clinic that I have targeted this drug to only people who have a heavy symptom burden, as just an example. In this analysis that you put together, did you find that people were generally only using the drug in patients who had a heavy symptom burden, or was it more broad in your analysis here?

Rana Mckay: I think it was more broad in our analysis. And I think also there were other variables too, in that patients were receiving concurrent—a subset of patients were receiving concurrent RPs as well. Whether they were on a prior RP, and then the radium was layered in, or whether they started the two together, or whether they were on the radium and then had the RP layered in later. I think we actually saw the whole spectrum of utilization concurrently with RPs.

And I think when we look at the PEACE III data, this was like practice-changing, like level 1 evidence of the efficacy of enzalutamide with radium-223. I know, granted, it was conducted in a patient population that never received an RP for mHSPC. But we saw pretty tremendous—the overall survival is still immature, but to see an overall survival of greater than 40 months in the mCRPC setting is pretty astounding.

So I think for an individual that has bone-predominant disease that hasn't been escalated in frontline, I definitely think that is a combination that should be considered and should be evaluated. So I do think it's important to think about earlier utilization, especially in people who are minimally symptomatic but have a high burden of bone disease.

Alicia Morgans: Great. Well, for your systematic review, what is really your thought? What message should people be taking from this? Because like you said, it's just the largest compilation of data that we've had, and really, I think, reflective of years of having access to this treatment.

Rana Mckay: I think the biggest thing that it highlights is really the survival benefit of early radium-223 use and actually appropriate patient selection to ensure that patients can actually receive five or more doses of radium—taking a look at their hemoglobin parameters, their neutrophil counts—to ensure that they're actually able to get through all six cycles. Because people who are able to get through all six cycles actually fare the best.

And then as we've continued to see with radium and the radiopharmaceuticals in general, the concurrent use of bone-protecting agents is really critical in this population. So I think those are the key take-homes.

Alicia Morgans: Absolutely. And I guess just one more question for you as you're thinking about sequencing—radium has sort of an opportunity to treat these patients who have bone-predominant metastatic disease, and I often am thinking about, to your point earlier, how do I get this patient all of the options that might be available? And sometimes I'm trying to play this chess game, inserting it here or there. Is that something that you do in your practice, and do you have any guidance for clinicians who are trying to play those same games and trying to ensure that patients have access to all of these treatments?

Rana Mckay: Oh, 1,000%. I think we all sit and strategize around how are we going to make sure to get all the life-prolonging therapies in. And so I think now with lutetium being available, post-chemotherapy in a broader indication, we certainly see people evolve. They may not start out their mCRPC course with visceral metastases but may potentially evolve into visceral metastases at some juncture down the road.

And now as people are kind of getting therapy escalated frontline, I think we're constantly strategizing around how to sequence everything. So I do think that earlier radium utilization allows for more effective treatment and more effectiveness of the treatment, and that you're actually able to get it all in.

I think what we're beginning to see now in late-stage mCRPC is, now with all the radiopharmaceuticals, chemotherapy, and people are just living longer, people's bone marrows get a little bit more beat up later on, and that becomes a real hurdle for getting various kinds of treatments. And so I do think that strategizing up front is a good thing.

Alicia Morgans: OK. Well, thank you so much for doing this work and for giving us some perspective—new information on a drug that we have experience with and I think are newly invested in and eager to think about again, especially with the PEACE III data. This is certainly a really helpful tool as we try to understand how to best think about this drug. So thank you for your time.

Rana Mckay: Of course.