Phillip Koo: Pleasure to be here. Thanks, Neeraj.
Neeraj Agarwal: So Phil, we have seen this radioligand therapy for now PSMA-617, lutetium-177, Pluvicto, is approved for metastatic CRPC setting in post-chemotherapy and pre-chemotherapy setting. And we really hope based on PSMAddition data that this will be an option for patients with metastatic hormone-sensitive prostate cancer setting. We also realize that based on multiple, not one, multiple real-world studies, that most patients with metastatic CRPC in our country do not receive more than two lines of therapies despite so many therapies being available.
So, my first question to you is, how do we make sure that our patients have the availability and option of getting this treatment? Because we know when disease progresses, they don't have time to get a PSMA PET scan and then start the insurance pre-authorization for Pluvicto. And it often happens, hopefully not very often in my clinic, but I do see patients losing their performance status because the authorization got delayed so much.
So, what are the practical insights from your perspective, having practiced as a nuclear medicine physician? What do you suggest we should do?
Phillip Koo: You know, you bring up a really important issue, this concept of, this idea of clinical implementation. You have these great drugs, lot of investment, with clear evidence that it shows it improves overall survival. So how do you get it into the right patients as soon as possible? And, in the end, there's so many different factors that come into play. Number one is just physical access. And if you think about, from when Pluvicto was first approved in 2022 till today, I believe there are actually over 700 or perhaps 800 sites throughout the United States that are now offering it. Doesn't mean it's always easy for patients to get it, but at least it's being offered and there are sites close to patients. I believe maybe 90% of patients live within 30 miles of a site that potentially could give the drug.
Neeraj Agarwal: Which is great news for patients.
Phillip Koo: It's amazing.
Neeraj Agarwal: Yeah.
Phillip Koo: But there's still other barriers. There's insurance barriers, because insurance, some systems might be closed, some might be open. There's pre-auth issues and there are logistical issues which you've brought up as well where a PSMA PET. And what we're seeing right now is, there's an increased utilization rate of PET-CTs. So, the question becomes, do we have enough PET-CTs out there? So, that's one. We see numbers of those scanners going up, utilization rates of PSMA PET going up. Then the question becomes, do we have enough readers, radiologists, and nuclear medicine physicians to read these in timely fashion? And we all know right now there's sort of a backlog and I think I could attest to at least stories I've heard where there are often significant delays not only in getting the exam done but getting the report with the findings from the exam.
So, all these things that might sometimes seem trivial are such an important piece that needs to be looked at. It's a challenge. I think there's a lot of hope and promise in the future, whether we're talking about AI and whatnot, but there are little things as well that we can do to help improve that whole workflow. And, oftentimes, I think, and in the end it really comes down to education and that's why I'm really honored to be here because physicians, providers need to learn, and the minute they think their patients might be a potential candidate for Pluvicto or some sort of, in this case Pluvicto, I think it's really important to sort of start thinking ahead, planning ahead. And that probably includes getting a PSMA PET earlier. Maybe you ordered ahead of time knowing that, all right, you want to see those results. See if they might be eligible, and if they are, get them queued up and ready to receive that drug.
Neeraj Agarwal: That's a great point. Patients on ARPI, if you just think about PSMAfore approval, PSMAfore-based approval, post-ARPI. Patients don't progress in a ARPI overnight. Most patients don't. They have slowly progressing PSA level. So, my strategy has changed in my clinic. If I'm planning to use Pluvicto in my patient, I don't wait for the last minute radiographic progression. I get the PSMA PET scan done when there is a slight increase in the PSA. So, by the time even there is an insurance delay, I have two or three months to get the PSMA PET scan done, get the report ready. And, by the time it is time to switch treatment, based on a more rapid PSA increase or based on radiographic progression, I'm ready because I don't have to now wait for PSMA PET scan to be done.
Phillip Koo: I think that's a great strategy because you're right, that slow rise in PSA is telling you something and it's giving you time to get prepared, and time is so important. And to be able to start that process and be able to know you have it ready when needed, because actually the actual treatment itself these days, the logistics, the infrastructure is there. So, you can get access to the drug pretty quickly and get that to your patients.
Neeraj Agarwal: And I have realized that once we allow our patients to clinically progress or radiographically progress, there's a high chance that we will lose the patient to progressive disease. Real-world data from multiple studies show that most patients with metastatic CRPC do not get more than two lines of therapies. I think that is happening primarily because our patients lose their will to fight or lose their performance status and they succumb to their disease.
Phillip Koo: I remember hearing that statistic and it really broke my heart to think that they only get two lines of therapy, and we know all these different drugs have shown a survival benefit alone. So, in many ways, the goal should be how do we make sure they get as many of these treatments as possible? And you're right, that's the goal.
Neeraj Agarwal: So, switching to the monitoring part, once you start Pluvicto or Lutetium-177-PSMA-617 and say patient came to my hospital, received the first dose, I have got PSMA PET scans, CT and bone scans. In real-world, when it is difficult to get the first PSMA PET scan done, how do we envision that patients will be able to continue repeating PSMA PET scan every six to 12 weeks and then SPECT scan, which is so easily available in many high level cancer centers, tertiary cancer hospitals, but you look at the real-world setting, we don't have sufficient number of radiologists or nuclear medicine physicians to even read those scans. Forget about getting those every six weeks or 12 weeks.
So, yes, the real-world is... The ideal world is that we need to be getting PSMA PET scan every so often, every three months, say, for example, or getting CT and bone scans and then SPECT scans on the bone scans to make sure.
But most of my patients, most of our patients in the US talking about as a country may not have that luxury to get those scans. So what do you suggest we do for those patients, for those physicians who don't have access to esteemed radiology colleagues and those scans?
Phillip Koo: There's so much variability in this topic right now and I'm going to have a different perspective on it. I actually think getting PSMA PET to follow these patients is too much. I think PSMA PET is really used to identify which patients would benefit. I think the follow-up can be done in a variety of ways.
In a lot of large perhaps academic medical centers, SPECT-CT is something that they'll use after injections just to see because you get a lot of information from that. That being said, I don't think you need a SPECT-CT after every cycle. There's some protocols where they might do it at baseline, perhaps after the third and after the final.
There's different approaches as well. I think following them clinically is really powerful. Monitoring the PSA closely, monitoring them clinically, other markers, and at signs of potential progression, sometimes contrast-enhanced CT can give you a lot of great information. They might have developed visceral metastatic disease in the interim, which would obviously inform how you manage that patient next.
So, I think there's a lot of different ways to approach it. I still think probably the best way is probably PSA clinical follow-up, and if there's suspicion for something more, then you trigger imaging. PSMA PET, it's great if you could use it all the time. And I think, at some point, we will get to the point where you are using PSMA PET perhaps every three months, six months to follow-up patients. I just don't know if that's the right use of resources today.
Neeraj Agarwal: Very well said. PSA levels actually correlate with the response on PSMA PET scan. And yes, of course, there are going to be some patients who are going to have neuroendocrine differentiation or where PSA may not reflect the responses seen on the PSMA PET scan, but most patients, would you agree, will have pretty good correlation of PSA response and PSMA PET scan response.
Phillip Koo: Absolutely. And that's where this idea of physicians... That interaction, seeing the patients in person, it's so important. And you as a medical oncologist who's seen endless numbers of patients, you know when these patients have a more aggressive variant, you could smell something going wrong and that neuroendocrine differentiation, yes, is a challenge. I will hope that in the near future we have better tools to document it sooner, but for the time being, great physicians are great. And I think that's another way to follow patients closely.
Neeraj Agarwal: And most of our medical oncology colleagues, they see so many different types of cancer and they rely on CT and bone scans, the traditional scans every three months. And if, I would say, based on what I've heard from you today, if we don't have SPECT scans and PSMA PET scans, we shouldn't worry about... We should not let that aspect not use lutetium therapy.
Phillip Koo: You're absolutely right. I believe in the SNMMI guidelines that we published maybe a year, maybe two years ago, we actually recommended contrast-enhanced CT as the primary tool to follow patients. And it's really that patients developing liver disease, liver mets, or visceral mets that contrast-enhanced CT does a great job.
Neeraj Agarwal: Well, thank you for sharing your insights on how to create better access of these life-prolonging therapies for our patients and how to monitor them once we have started them on treatment with Pluvicto or for the sake of completeness PSMA-617-lutetium-177.
Phillip Koo: I love it. Thank you very much, Neeraj.