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Safety and Dosing of Lutetium-PSMA in the Pre-Chemotherapy PSMAfore Trial - Oliver Sartor

November 3, 2025

Zachary Klaassen speaks with Oliver Sartor about safety and dosing in the PSMAfore trial examining lutetium PSMA-617 in metastatic castration-resistant prostate cancer. Dr. Sartor explains that PSMAfore patients, who progressed after androgen deprivation therapy and one androgen receptor pathway inhibitor without prior chemotherapy, represent an earlier disease stage than VISION trial patients. The PSMAfore population demonstrates improved tolerability with fewer adverse events and cytopenias compared to the heavily pretreated VISION cohort. The FDA-approved dosing is 7.4 gigabecquerels every six weeks for six treatments, though optimal dosing may vary based on bone disease burden and volume. In clinical practice, patients frequently request Pluvicto™ and prefer it over chemotherapy. Dr. Sartor emphasizes confirming PSMA PET positivity and evaluating cytopenias and renal function before treatment. 

Biographies:

A. Oliver Sartor, MD, Director, Transformational Prostate Cancer Research Center, East Jefferson General Hospital Cancer Center, Tulane University Cancer Center, New Orleans, LA

Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor of Surgery/Urology at the Medical College of Georgia at Augusta University, Wellstar MCG, Georgia Cancer Center, Augusta, GA



Related Content:

Results from the Phase 3 PSMAfore Trial in Metastatic Castration-Resistant Prostate Cancer - Karim Fizazi

The PSMAfore Trial and its Role in Shaping Future Prostate Cancer Treatments - Oliver Sartor

PSMAfore Trial: Lutetium PSMA's Impact on mCRPC Quality of Life - Karim Fizazi

SUO 2022: Theragnostics: The VISION Trial and Beyond
Read the Full Video Transcript

Zachary Klaassen: Hi. This is Zach Klaassen for UroToday and I am delighted to be joined by Dr. Oliver Sartor, who is a medical oncologist in New Orleans, Louisiana. Today, we're going to be talking about PSMAfore and really digging into the safety, the dosing, and the toxicity profile. So nobody better to talk about it than you, Oliver. Thanks for joining us as always on UroToday.

Oliver Sartor: Nice to be here, Zach. Really delighted to be here at PCF 32.

Zachary Klaassen: Absolutely. And if we look at level-setting for our listeners about PSMAfore, just tell us the population, the high-level outcomes, and that'll get us into our discussion about safety and dosing.

Oliver Sartor: Yeah. So super easy, really. The VISION trial was the first one and these are patients with metastatic CRPC, PSMA PET-positive disease that progressed after ADT and at least one ARPI and at least one taxane. The truth is many of them had progressed after two taxanes and two ARPIs.

Zachary Klaassen: Right.

Oliver Sartor: Pretty advanced disease. In the control group, we're talking about a median survival of about 11 months.

Zachary Klaassen: Yeah.

Oliver Sartor: So here, in PSMAfore, these are patients who've failed or progressed on ADT and an ARPI, metastatic CRPC, but now the median survival is about two years in the control group.

Zachary Klaassen: Right.

Oliver Sartor: And so these are patients who are pretty favorable as a whole compared to the VISION patients. No prior chemotherapy allowed.

Zachary Klaassen: That's perfect. And I think if you look at the VISION criteria, which you nicely laid out, versus the PSMAfore patients, how does the toxicity profile of the AEs compare between those two trials?

Oliver Sartor: Well, guess what? When you have less disease, you have fewer AEs and that's one of the things we actually picked out pretty clearly. If you looked at disease burden in the bone, guess what? You have more myelosuppression if you have more bony disease. So these things kind of go together. And it makes sense. The patients are in better performance status, able to tolerate the ADT and ARPI pretty well.

Zachary Klaassen: Yeah.

Oliver Sartor: They're also able to tolerate the lutetium pretty well and these patients really do amazingly well. The vast majority get six treatments. And that's what was prescribed: six treatments and go on from there.

Zachary Klaassen: That's a perfect dovetail to my next question. What do you think is the optimal dosing schedule for these patients? There have been a couple other trials that have looked at this. What are your thoughts on number of visits and the dose given at those visits?

Oliver Sartor: Zach, it's a more subtle and a better question than you might think because we have an FDA-approved 7.4 GBq every six weeks for six doses. Okay. That's what's in the label. Do we know that that's optimal? Well, it turns out with Scott Tagawa that I've actually given 22.2 GBq over 15 days, which is a totally different dose, and we've also stretched it out a little bit. So there hasn't been a lot of dosing schedule exploration. What I'll say is that we do have a schedule that works. What's optimal could be dependent on the individual patient and what's optimal could really vary and depend on the degree of bony metastasis, high-volume, low-volume, node-only disease. There are a lot of things we don't know.

Zachary Klaassen: Sure.

Oliver Sartor: So I hate to be dogmatic. I'm just going to say this works, but there's more to the story.

Zachary Klaassen: Yeah, absolutely. In your practice over the last six to seven months since approval based on the PSMAfore indication, what have you seen in uptake in terms of patients asking about it? Are there different AEs that you've seen in PSMAfore versus VISION? What's the feedback been from a patient standpoint?

Oliver Sartor: Yeah, the patients are very interested in getting it. They're not that interested in getting chemotherapy. They are aware of the FDA approval. They come in asking for it. And they oftentimes are missing some of the particulars. They don't know how many doses, what the frequency is. They say, "I've heard about Pluvicto. I'd love to have the chance to do it if I'm one of those patients that could receive it."

Zachary Klaassen: Yeah.

Oliver Sartor: And then I'll say, "Well, look. We got to check the PSMA PET."

Zachary Klaassen: Sure.

Oliver Sartor: We have to look at your cytopenias, make sure your hemoglobin's okay, white blood cell count's okay, look at your renal function. Go ahead and do the check and make sure you've had an ADT and an ARPI.

Zachary Klaassen: Yeah.

Oliver Sartor: So we just kind of run through a little checklist and if they're appropriate, then we often put them on Pluvicto and go from there.

Zachary Klaassen: Awesome. Last question from my standpoint: when we look at the post-VISION criteria, patients who have obviously had docetaxel, are you seeing fewer cytopenias with patients that have just progressed on ARPIs?

Oliver Sartor: Yes.

Zachary Klaassen: Okay.

Oliver Sartor: Yes. There are a couple of things that are important here. Number one is in the VISION population, 100% of the patients had chemotherapy.

Zachary Klaassen: Yes.

Oliver Sartor: And 40% of the patients had two chemotherapies.

Zachary Klaassen: Good point, yeah.

Oliver Sartor: So they would have had docetaxel and cabazitaxel. Furthermore, you start looking at how far along they were. I talked about the control group having a median survival of 11.3 months.

Zachary Klaassen: Right.

Oliver Sartor: If you look at PSMAfore, the median survival was about 24 months. So these are patients with more advanced disease, more heavily pretreated. And guess what? They get sicker faster, they have more AEs, are more prone to have cytopenias and other breakdowns. That's inevitable. We know that from oncology. Sicker patients are more likely to have worse AEs.

Zachary Klaassen: Right. Absolutely. Any take-home messages? Anything we haven't hit on for our listeners?

Oliver Sartor: I think we need to stay tuned. We've just presented the PSMAddition trial and there we have a hormone-sensitive population with six doses. We don't have adequate maturity right now, but the preliminary data show it's a positive trial. rPFS was 0.72, which clearly met the predefined endpoint. Overall survival was 0.84, which is also favorable, but relatively immature. So we've got a real therapy here. We just need to learn a little bit better about who to give it to. And we still have more work on the dose and schedule. I'm okay to say that. But I'm going to simply say that we made a lot of progress with a tolerable therapy that men are happy to get, and it's not chemotherapy, and men don't like chemotherapy.

Zachary Klaassen: Yeah. Well said. Thanks so much as always, Oliver, for joining us.

Oliver Sartor: Great. Thanks, Zach.