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Implementing Lutetium-PSMA — From Trial Design to Operations - Oliver Sartor

November 3, 2025

Zachary Klaassen hosts Oliver Sartor to discuss the real-world implementation of lutetium PSMA-617 following PSMAfore trial approval in the pre-chemotherapy metastatic castration-resistant prostate cancer setting. The trial demonstrated radiographic progression-free survival of approximately 12 months versus 5.6 months with androgen receptor pathway inhibitor switch, yielding a hazard ratio of 0.43. Dr. Sartor describes strong patient interest in accessing Pluvicto™ earlier than the previous VISION indication required. Community implementation requires specific infrastructure including an authorized user for radioactivity injection, radioactive waste disposal capabilities, and a radiation safety officer. Many large urology group practices are establishing administration protocols, with processes often synergistic with existing radium-223 infrastructure. 

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:

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

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
Read the Full Video Transcript

Zachary Klaassen: Hi, my name is Zach Klaassen, urologic oncologist at the Georgia Cancer Center in Augusta, Georgia. We're on UroToday with Dr. Oliver Sartor, who is a medical oncologist in New Orleans, Louisiana. Today we're going to be talking about the new PSMAfore indication for lutetium, specifically looking at real-world implementation in the community. So Oliver, as always, you're the expert on this topic. Thank you for joining us.

Oliver Sartor: Oh, thanks for having me, Zach.

Zachary Klaassen: So just level-setting for our listeners, again, the entry criteria for PSMAfore and what the high-level results were.

Oliver Sartor: Sure. Let me give a little bit of history first.

Zachary Klaassen: Yeah, absolutely.

Oliver Sartor: So the first trial that was positive for lutetium PSMA was called the VISION trial. These patients had to have ADT, an ARPI, and at least one chemotherapy. And many of the patients, in fact, had two chemotherapies and two ARPIs. So pretty advanced patients. We got the overall survival benefit in the VISION study.

Well, then we said, "Well, wait a minute. We don't want to wait until everybody gets chemotherapy. Let's go a little bit earlier." So we went to the ADT-ARPI-experienced group, CRPC, PSMA PET-positive, no prior chemotherapy. So now it's one prior ARPI, and they did an ARPI switch versus the combination of lutetium PSMA-617, just like we always do. So it was Pluvicto versus ARPI switch. We had a primary endpoint of rPFS, radiographic progression-free survival. Clearly positive. It came in at around 12 months. And the control arm was around 5.6 months. The hazard ratio was approximately 0.43, so really blazingly positive.

We did have a crossover design and patients on the control arm, if they had not received Pluvicto, then they could get the lutetium at the time that they progressed. And it turned out that the vast majority did. So that confounded the overall survival analysis, and the final overall survival was 0.91. But nevertheless, it's a positive trial, it's FDA-approved, and patients are very interested in this pre-chemotherapy space.

Zachary Klaassen: Absolutely. And we're coming up on almost seven months since approval. This was March 2025. And so, in your practice, and maybe just what you've heard from the community, how has it been in terms of implementation into practice and real-world experience today?

Oliver Sartor: A lot of interest in the trial. People were aware of Pluvicto. In fact, I was maybe a little frustrated that they weren't able to get it in the upfront setting. So people came in and they'd ask, "Okay. You mean I have to have chemotherapy before I can get it?" And the answer is now no. So it was a little bit of a transition, just understanding the change in indication. We still have people who want Pluvicto too early. They want it even before the hormones. We don't have data in that setting. But I'll simply say that in this metastatic CRPC setting, post-ADT and an ARPI, PSMA PET-positive, we have a nice population and patients definitely want to get it. And the community centers are giving it as well, which is great. We can't give all the Pluvicto in the world.

Zachary Klaassen: That's right.

Oliver Sartor: I'm delighted to have partners out there who are able to administer it. And the truth is, it's a very safe drug. The number of dose delays and dose problems that result in holdings or problems with having to drop doses is just negligible. It's very small. So the bottom line is this is a safe drug and particularly in the PSMAfore setting, it's particularly safe. Because these patients are not beaten up with chemotherapy and don't typically have high-volume disease.

Zachary Klaassen: Yeah, great answer. I think, focusing again on that community setting, so we know, let's say somebody wants to get started at their cancer center three hours from New Orleans. What sort of credentialing, what sort of maybe reimbursement challenges, if any? What's that setup look like for a center that's looking to get involved?

Oliver Sartor: Well, the first thing you really have to have is an authorized user. This is somebody who can inject the radioactivity, somebody who's typically either nuclear medicine or radiation oncology. You have to have radioactive waste disposal. You can have a little radioactive waste. You probably need to have a radiation safety officer, and they don't need to be there every day, but they can stop by and do your certifications. You need to have processes in place so when you're giving the therapy, you know exactly what you're doing. When you're discharging patients and if you have the waste, you'll need to be able to monitor it and make sure that it's disposed of at the proper time.

So it takes a little bit of work. But there are actually, I've seen YouTube videos where people have begun to do this. A lot of the LUGPA, the Large Urology Group Practice Association, practices are starting to look at the administration of Pluvicto and other isotopes. And by the way, people have already set up for radium-223 as well. So these are somewhat synergistic. If you satisfy the radium-223 criteria, you may be satisfying the criteria for Pluvicto.

Zachary Klaassen: Excellent. And anything you've heard in the community specifically about reimbursement issues? Or is it that now that we've got good data, we've got FDA approval, has that been a problem?

Oliver Sartor: We're working through it. And it turns out that some of the things could be pretty tricky. The Novartis team has people to help.

Zachary Klaassen: Excellent.

Oliver Sartor: And they're willing to help guide you through the process. So inevitably people are going to make some mistakes early on, and we just want to make sure that those mistakes don't hurt too badly. So having help and somebody from Novartis at your back is really a good thing.

Zachary Klaassen: Awesome. Final question, kind of a two-part question. We've seen now recently, as of last weekend at ESMO, we've seen this moving up a little bit further into the mHSPC setting with PSMAddition. So I just want to get your quick thoughts on that and maybe some of the new agents you're looking forward to that are coming down the pipeline.

Oliver Sartor: Yeah. So I just presented the metastatic hormone-sensitive prostate cancer study, and it is called PSMAddition. I just presented that at the PCF 32nd Annual Scientific Retreat. I'll simply say that it's got a positive trend. It's a relatively immature trial, but so far the hazard ratio on rPFS is 0.72. The hazard ratio on OS is 0.84. Going the right way. Safety to me is fine. I don't have any safety issues. So, so far so good. We need more follow-up.

Zachary Klaassen: Okay.

Oliver Sartor: Other things I'm interested in, we've got some really provocative T-cell engagers for the first time, and one that has caught my eye is called pasritamig, and it targets KLK2 by CD3. They've got an outpatient regimen and there are a series of phase III trials that are now being organized. And then you start looking at STEAP1, which is another CD3 T-cell engager. We're going to have more therapies fairly soon, and that's good for our patients.

Zachary Klaassen: Absolutely. Always enjoy the conversation. Any take-home messages, anything we haven't hit on you want to share with our listeners?

Oliver Sartor: Learn about Pluvicto. Your patients are probably interested. And my advice is bring it into your practice and be able to offer it for those patients that are appropriate.

Zachary Klaassen: Wonderful. Oliver, thanks so much, as always, for your time.

Oliver Sartor: Great. Thanks, Zach.