Zachary Klaassen: Hi, my name is Zach Klaassen. I'm a urologic oncologist at the Georgia Cancer Center. We are on UroToday at ASCO 2025 in Chicago. I'm delighted to be joined by a good friend, Dr. Jack Andrews, who's a urologic oncologist at the Mayo Clinic, Arizona, and Emy Ahmed, who is a research fellow at the Mayo Clinic. Thank you both for joining us on UroToday.

Jack Andrews: Thanks, Zach. We're really excited to be here.

Zachary Klaassen: There's been so much RLT at ASCO and even leading up. And you guys have a really nice study, looking at what's the impact of giving Pluvicto late or early after chemotherapy. So Jack, I'll start with you. Just bring us up to speed briefly on the journey over the last four or five years to get to this point.

Well, lutetium-177 PSMA and theranostics is really exciting for both clinicians and patients. We see patients asking about it all the time in every setting. VISION was published and got FDA approval for use a couple years ago and showed that in the late mCRPC setting, post-docetaxel and androgen receptor inhibitor, that there was a survival advantage.

And what we've seen since that time is a hard push to earlier disease settings with different prior therapies. And now we're also seeing additional theranostics that aren't just Pluvicto, but other investigational drugs, and then, potentially, the role of different dosages, and timing of sequence of Pluvicto.

So it's a really exciting time, and we're going to learn a lot over the next five years, I believe, when it comes to theranostics. And it's a drug that doesn't tap into the androgen receptor pathway and gives us a whole new way to treat prostate cancer. So I think it's just a really exciting time for clinicians, but also a really good time for our prostate cancer patients.

Zachary Klaassen: No doubt. I think it's been so much excitement in the last five years. Still feels like early days, though, doesn't it? The next five years are going to be incredible. Let's talk a little bit about your guys' study. So what was the objective and rationale for looking at post-chemo, early versus late treatment?

Eman Ahmed: So since, there have been a lot of trials trying to push lutetium early in treatment algorithm. We wanted to evaluate lutetium, the timing of lutetium in both the chemotherapy setting and two groups of patients, whether it's administered early versus late and its impact on PSA response.

Our primary endpoint for PSA response is to be 50% reduction in PSA value after lutetium therapy. And that's our primary point for abstract. So when we run the analysis, the p value was not significant between the two cohorts. So the PSA response was similar in both groups of patients. This can tell us lutetium is still effective, whether it's administered early or late.

Zachary Klaassen: Absolutely. I think you think about-- patients are asking. I just had chemo, whether I'm three months, six months, 12 months. Your data says it doesn't really matter. You can still get a benefit from Pluvicto, even several months after chemotherapy.

Eman Ahmed: Yeah, the first group received allocation within three months after chemo, versus the second group received it after three months. And they have comparable or similar PSA response. So there was not a significant or big difference in their PSA response.

Zachary Klaassen: That's great. Did you guys look at tolerability outcomes, or was it more so just the PSA response?

Eman Ahmed: No, till now, we looked into their PSA response. But we're still working on these patients.

Jack Andrews: And that's something we'll look at. And in further studies, we'll look at overall survival. I think one of the impetus of this study was the hypothesis that maybe men who are treated with docetaxel and shortly after progressed to needing Pluvicto, that their disease might be in a stressed state, that maybe they're going to respond better to lutetium. And we wanted to compare them to men who had a longer interval between docetaxel and their next line treatment with Pluvicto.

And those men, that would be a positive prognostic factor. You would expect those men to do better. And so we found that there was no difference in the outcomes in PSA response, and we'll look at the overall response.

And so I think that gives us some reassurance that we can use Pluvicto, whether it's a short interval or long interval. And maybe the fact that there are similar outcomes does give some credence to this hypothesis. Certainly doesn't prove it.

But that docetaxel, in short order, followed by Pluvicto, may be a synergistic effect. And this study was designed and submitted to ASCO prior to the FDA approval for Pluvicto in the first line mCRPC setting. And so that's really the next step where we're interested, because I think we're going to see a lot more patients getting Pluvicto.

And for the men getting triplet therapy, I think Pluvicto first line mCRPC is going to be the standard of care because we've really used our ARI and our docetaxel right away. And so I think this same question in that patient population is very interesting, and that's what we're looking at right now. And I think that'll hopefully show or tease out some of these results, even further.

Zachary Klaassen: It's a great point. The last two months have been crazy. We've had the PSMAfore approval, as you mentioned, pre-chemo. FDA approved, two weeks later, NCCN guidelines update. And just two months later, we're dealing with this whole new denominator of patients.

So I think your point about the triplet therapy in the metastatic hormone sensitive setting is interesting because these are going to be patients that probably are younger, probably come in with a really high disease burden as we move forward.

That's who we're going to select for triplet, and then they're going to be candidates straight off the bat for Pluvicto, or even if they're getting a doublet therapy. Now we can give them. So this whole space is going to continue to evolve over the next several years.

Jack Andrews: And that's what makes this interesting in advanced prostate cancer. Probably more so than any other cancer, it's a puzzle that we have to put together. And the sequencing of treatments, and when you use these treatments, and what do you have left for later line therapies, it really is going to matter.

And so it's really exciting, it makes it challenging because there's only so many patients that we can get on trials, that we can try these different avenues. And there's thousands of ways that we can get to fifth-line treatment. But it's really exciting. And overall, it's a good thing for patients.

Zachary Klaassen: Absolutely. And Emy, a concluding statement or two.

Eman Ahmed: So I think, as Dr. Andrews mentioned, it gives reassurance for the provider if those patients receive the lutetium early, versus the other group of patients who will receive lutetium late. They can still benefit from lutetium. So lutetium is effective in both cohorts on both ways. So it doesn't matter the timing of lutetium, it will still work better for all patients.

Zachary Klaassen: It's a great concluding statement. Congratulations on the work you guys have done, adding to the tidal wave of RLT at ASCO. And thank you for joining us on UroToday.

Jack Andrews: Thanks so much.