Pluvicto in Metastatic Hormone-Sensitive Prostate Cancer
Patients with prostate cancer that has spread now have a new treatment option to consider.
The FDA has expanded its approval of Pluvicto® (lutetium Lu 177 vipivotide tetraxetan) to include metastatic hormone-sensitive prostate cancer (mHSPC). This type of prostate cancer is also called androgen pathway modulation-naïve or sensitive (mAPMN/S).
PCF’s Dr. Phillip Koo speaks with leading experts to explain what this could mean for you or a loved one. You’ll learn about:
- How radioligand therapy works
- How you know if you may be eligible
- Patient experience with treatment, side effects, and radiation safety
- How you and your doctor can consider Pluvicto in the landscape of treatment options for mHSPC
- Questions to ask your doctor
Read the Transcript below:
Phillip Koo, MD [00:00:00] The FDA has approved Pluvicto for a new group of patients with prostate cancer. Here’s what that actually means for you, or someone you love. It’s so, so exciting to be here joined by this great group of experts to talk about and celebrate a new indication for Pluvicto. It’s interesting looking back when this drug was first approved in 2022 and Oliver and Kendra, I believe we were together in New Orleans for that landmark day. And then it’s interesting to fast forward a few years in 2025 when it was then approved for a pre-chemo application indication and now, we have a new indication for Pluvicto, but before we get into it Gordon, give us sort of a one sentence overview of what is Pluvicto?
Gordon Brown, DO [00:00:48] So, thanks for having me, Phil. Pluvicto really is another great example of precision medicine in the management of patients with advanced prostate cancer, and specifically, this is a targeted radiation-based therapy which binds specifically to prostate cancer cells in patients with advanced prostate cancer and delivers a small radioactive payload to kill those cells.
Phillip Koo, MD [00:01:10] You know, it’s pretty novel and it’s great to see that, you know, that technique works. So, we now have this new approval. What does that mean for patients? What is the approval and what does it mean for patients?
Gordon Brown, DO [00:01:23] Well, it certainly expands our current armamentarium of managing a patient with advanced prostate cancer. We now have approval in patients with hormone-sensitive metastatic prostate cancer, and that patient population really consists of two general groups of patients. The first patient is that patient that comes in with a new diagnosis of prostate cancer who has evidence of disease outside the prostate gland or is metastatic at the time of diagnosis. And this approval also applies to the group of patients in whom they’ve had definitive local therapy or prior therapy and unfortunately have a recurrence of their disease in the metastatic setting and have PSMA-avid findings on their recent PSMA PET scans.
Phillip Koo, MD [00:02:10] So Kendra, we’re gonna turn it over to you. You know, Gordon gave us a great overview of what simple, you know, in very basic terms of what Pluvicto is. Sort of let’s dive a little deeper and tell us about the mechanism of action and how exactly it works in more detail.
Kendra Harris, MD [00:02:25] Sure. So, I think the bottom line is to think about it according to the following process, which is if you can see it, then you can treat it. And this approach, Pluvicto’s mechanism, is an approach that first makes use of imaging, and in particular PET scans, and uses a surface signal that prostate cancer cells and prostate cells can fly on their surfaces. And that PET scan recognizes that surface molecule and sends an imaging signal back. And so many patients, either for the first time or as part of their follow-up for where they’re at in their disease, will get these PET scans that are represented with colors to show you where the prostate cancer is. And the critical jump from that to the treatment is you keep that homing beacon and keep that recognition of that very particular flag, the PSMA, but instead of attaching it to a molecule that lets you see it, you swap it out and instead put a radioactive molecule that can actually deliver lethal damaged cancer cells. And so, it’s a, if you can see it with your PET scan, then you can treat it with a radioactive isotope. In this case, the isotope is called Lutetium.
Phillip Koo, MD [00:04:06] I think a lot of times patients hear about it, and they get a little sort of overwhelmed because they hear radiopharmaceuticals, nuclear and terms like that. Sort of just break it down and just explain to patients exactly what the workflow might look like.
Kendra Harris, MD [00:04:18] So the first essential step is to meet a provider with experience managing advanced prostate cancer, whatever their credentials are. The second is to have a PET scan, PSMA PET scan done to demonstrate that you have disease that can be seen using that tool. It’s also wise to ensure that you don’t have any visible areas of disease that don’t sort of react to this particular imaging agent. And then you establish with a physician that has a process in their clinic to prescribe this medicine.
Phillip Koo, MD [00:05:02] How many doses, how are they spaced apart and how long are patients in your clinic before, from the time they step in to the time the leave?
Kendra Harris, MD [00:05:12] So. The processes is that I would order this medicine, take somewhere between one and two weeks to get in the line to receive it. The actual administration takes less than a minute, minute, two minutes. It’s actually administered in our clinic just with an IV push. And after the administration, the patient is assessed for suitability, the IV is removed, and then they go home. So probably the whole visit is maybe 40 minutes, with the administration happening at the end. Patients are given six doses of Pluvicto once every six weeks, assuming that their lab work looks favorable. And after the sixth dose, they are referred back to my colleagues and also followed in my clinic.
Phillip Koo, MD [00:06:05] In general, what types of instructions are you giving patients and their loved ones regarding radiation safety?
Kendra Harris, MD [00:06:11] I always remind patients that you can think back to COVID days. That they want to have six foot of distance when they’re spending periods of time around people for the first couple of days around their treatment. We ask patients to sleep separately from their spouse for a couple of days. It’s really about time and distance. These precautions are easily achievable, and we give them to patients in a printed form. But it’s very common for patients to be very scared and for their families to be very scared. So, we also provide educational sessions for those spouses, patients, or families that have additional questions.
Phillip Koo, MD [00:06:57] Talk to us about the side effects. What side effects are we seeing that might occur and may be different than the other patients that might have been treated in the different studies.
Oliver Sartor, MD [00:07:08] One of the things a little bit unusual is you can get some dry mouth. If you looked at a PSMA PET scan, you may notice that the salivary glands have a lot of uptake, and that’s going to be true when you inject lutetium as well. They end up coming into the salivary glands at a rate kind of out of proportion to what you might anticipate. But the side effects are typically a dry mouth that is pretty mild. These are grade one, rarely grade two. And that means you might have a little need to drink some more water. Maybe you use some lemon drops or lozenges. There are some things that can happen. But that happens, you know, almost about half the time. But it’s not a surprise because it happened in the other settings as well. Now you can get a little more fatigue. It’s one of the things that could happen. Typically, that’s transient. But most people are not really having much in the way of side effects that would prevent them from having a normal life. In fact, there’s a lot of patients feel better. Because they’re getting their cancer treated. And so, they can go home and be very active and participate in their work life, their family life. Once they get over that short period of kind of radiation isolation, if you will, kind of like COVID, I like the way Kendra put it. And then you get back to normal. That’s the best news.
Phillip Koo, MD [00:08:29] Any advice that you have for patients walking into their visits saying, “Hey doc what about this PSMA PET? Should I get it?” Is that something that would offend you, or something you would encourage?
Gordon Brown, DO [00:08:39] No, I would encourage, and actually I find that patients for the most part come to these conversations much more educated, you know, through discussions like this than they ever have in the past. And really almost everybody that comes into this disease stage should have, I will argue everybody should have a PSMA PET as part of their initial evaluation and treatment planning to meet to determine eligibility. Not only for this therapy, but potentially for subsequent therapies and understand how extensive their disease is. So certainly, we wouldn’t be offended by that conversation and one that if it hadn’t been ordered, it certainly should be ordered at the time of that consultation.
Phillip Koo, MD [00:09:19] Oliver, in the entire metastatic hormone-sensitive space we’ve seen this disease state change so much over the past couple years and now we have another approval for another type of drug in this setting. What advice do you have for patients to figure out in conjunction with their physicians what treatments are best for them and where do you see this fitting?
Oliver Sartor, MD [00:09:40] Today, patients should get intensification with metastatic hormone-sensitive prostate cancer with one of these agents that we refer to, enzalutamide, abiraterone, apalutamide and darolutamide. They really all individually have been shown to have a very positive effect. So that’s one thing that’s kind of across the board. It turns out that there’s some other precision therapies we need to be aware of. For instance, In genomic testing we can sometimes find BRCA mutations and for patients with a BRCA2 mutation today there’s an FDA approved agent called niraparib that can be added to abiraterone and ADT and shows superior outcome. There’s also another class of patients called the PTEN-deleted group and PTEN is a particular gene that can be lost in a person to patients. And it turns out that there’s a new drug called capivasertib. We also have chemotherapy, and that’s an older therapy. It does have more adverse events associated, quality of life effects associated, but there is data to show that you can add in the chemotherapy, and that can also have a positive effect. So, patients coming in today have a variety of choices. I must admit – to me, this is the most important one that we’ve found, because you preserve the quality of life. And so many patients are eligible in this “see it, treat it” concept, which was alluded to by both Kendra and Gordon.
Phillip Koo, MD [00:11:17] Gordon, I’ll start with you. You know, the one patient population that might qualify are those who are newly diagnosed and they have metastatic disease at the time of diagnosis. Where in that patient population do you feel a drug like Pluvicto fits now that we have this indication?
Gordon Brown, DO [00:11:34] You know, as an example, I had a patient roughly about two weeks ago, 74-year-old patient came in markedly elevated PSA, went on to have a biopsy and diagnosed prostate cancer, had multiple PSMA-avid lesions or a positive PSMA PET scan and multiple bone lesions. And you know, he was somebody that as Oliver alluded to kind of started with that backbone of hormone deprivation and ARPI. But he was also somebody that was very adverse to receiving any systemic chemotherapy and probably could have benefited from treatment intensification in that setting based on how much disease he had demonstrated on his PSMA PET scan. He would have been the ideal patient, you know, for me to offer this type of treatment intensification, in lieu of systemic chemotherapy to improve his outcomes for this disease. And we see these, you know, we have these conversations and it’s really exciting now that we have another kind of tool in our toolbox to offer this patient population. He would have been really, to me a perfect patient.
Phillip Koo, MD [00:12:43] So we’ll start off with you, Gordon, as a urologist who sees these patients in the community setting in Jersey, patients who have metastatic hormone-sensitive disease, they have a scheduled visit with you coming up, they just saw this, they watched this webinar, how should they enter in your office, and what questions should they be asking?
Gordon Brown, DO [00:13:00] One, I think they should bring a caregiver. I think that that’s an essential part of this conversation is to come in with a care partner so that there can be multiple ears listening to that conversation. Secondarily, I think they have to have a conversation around their PSMA PET results and their potential eligibility for this therapy. And also, you know, kind of discuss and review their other potential underlying medical conditions, right, to see if something might preclude them from receiving a therapy like this. And then this really becomes a shared decision-making conversation very much, but an exciting one, because now we have really good, very effective options in the appropriate PSMA-avid patient to improve their care outcomes.
Oliver Sartor, MD [00:13:44] You know, you need to say, well, Dr. Sartor, um, help me understand what my treatment options are in this particular situation. I know it’s serious. I know it’s metastasized. I know I’m going to need treatment. Tell me what my options are. Is there anything else I should be considering that we might not be talking about today. And that way it kind of broadens out the conversation. You don’t want to, in my mind, sort of be too strong-handed with your physician by pushing one therapy or not. That doesn’t go over particularly well. But you want all the options to be considered. And that’s a critical part of the conversation.
Phillip Koo, MD [00:14:28] So Oliver, you’ve led multiple studies that have led to new drug indications new drug approvals The question that patients always have is now that this press release or this release is out. When can I start getting it?
Oliver Sartor, MD [00:14:40] It turns out that Medicare patients will probably have very, very rapid access. But as you go through the various Medicare Advantage plans, or maybe you don’t have Medicare, you’re on a commercial insurance, you’ll need to seek approval. We call that a pre-certification. And that pre-certification ensures that you will have the treatment paid for. Unfortunately, these treatments are expensive. And without the insurance approval, it would be an onerous task to ask people to pay for it out of pocket. So that said, I think one of the rate-limiting steps post-FDA approval is the insurance companies gearing up, recognizing the new FDA approval and responding to it in an appropriate way. It should happen instantaneously, but it doesn’t. And that’s going to be a little bit frustrating as patients hear about the approval. And then seek the treatment and then have to go through the pre-certification process that may be a little more delayed than what we would prefer. I promise you that your physicians will fight for your ability to get this therapy, but in the end, the policies of the insurance company will have to grind forward in a way that ensures that the approval’s actually paid for.
Phillip Koo, MD [00:16:00] Financial support is offered. I think Novartis has a patient support line that can offer some financial support in certain cases. And there’s numerous sites throughout the country that are now offering the drug. So hopefully access isn’t an issue and hopefully the whole payment piece gets resolved quickly as well.
Kendra Harris, MD [00:16:19] I think it is an exciting time where I think over the last five years, we have new domains of treatment. This molecular targeting of radiation was a new category. I don’t want to say it’s an embarrassment of riches, but as the number of options for what patients can receive increases, it becomes more complicated. And so, choosing the approach with the widest gap between how much it helps you and what the risks are. That’s the goal.
Phillip Koo, MD [00:17:01] Yeah, you know, I echo those sentiments. It’s such an exciting day. I think it’s a, it’s a victory for radioligand therapies. It’s a victory for precision medicine. Most importantly, it is a victory for patients, and we will be hosting another webinar later this year to really dive deeper into radioligand therapy, radiopharmaceuticals, just because so much continues to change and there still is so much more hope of what it could do in the future.