Oliver Sartor: Yeah, absolutely Phil, and honestly, I think it's very exciting. I think for some years now that we've established the effectiveness of ADT in an ARPI, drugs like the darolutamide, enzalutamide, apalutamide, abiraterone. And that has become an unequivocal advance in these metastatic hormone-sensitive patients. We could call them APMS if you want to use the new terminology. But the intensification studies previously had used docetaxel, but not really to show that docetaxel added the value to an ADT plus ARPI, but rather than an ARPI, specifically either abiraterone or darolutamide could add value to ADT docetaxel.
This is different. Here, the backbone is going to be ADT and an ARPI of choice for the investigators, metastatic hormone-sensitive prostate cancer, all of us know what that is, and intensifying treatment with the use of Pluvicto and a randomized phase-three trial with an rPFS and an OS endpoint. And guess what? We have a positive trial meaning that patients can have intensification of their ADT and ARPI with the use of Pluvicto. I think it's a very important step forward.
Phillip Koo: Thank you. That's really great perspective on that addition of this drug to ADT and ARPI. So what advice do you have for those physicians taking care of these patients with hormone-sensitive disease that's metastatic and how should they take into account those nuances and figure out which patients would benefit from this type of intensification?
Oliver Sartor: Yeah, great question. And we have a little complication, if you will, in this hormone-sensitive space. We have a couple of precision therapies that have now been approved by the FDA. For those with BRCA2 mutations, we have the addition of niraparib to an ADT abiraterone background. And we also have very recently have had a PTEN-selective group with a drug called Truqap, and that's also an interesting thing. The selection when it comes to the PSMA PET-positive patients is to do a PET scan with PSMA ligand and to show that you have uptake in a metastatic disease, and we know that those people who have uptake are more likely to benefit than not.
So that's absolutely an inclusion criteria, but I think it was extremely interesting. Fred Saad presented some data recently at the ASCO meeting in Chicago in which he looked at high volume, low volume, looked at individuals with de novo versus recurrent disease, and it was pretty remarkable that across the board there appeared to be benefit. So I think the key element is going to be in those that are PSMA PET-positive and a metastatic lesion, and particularly those you think might need intensification. One thing, and I'm going to extemporaneously speak here, not part of the trial, but part of my practice is to identify those individuals with oligometastatic disease and use metastasis-directed therapy in that setting. So I have a little bit of a dividing line between the oligometastatic and the polymetastatic, but those are my rules, not necessarily what the FDA said. [inaudible 00:04:14] PSMA-PET positive, then you can intensify with this approach.
Phillip Koo: So that's interesting, so ... All right. So logistically, if you have a patient who's metastatic hormone-sensitive, makes sense to get genetic testing, get tissue samples, do genetic testing, also get a PSMA PET, would you do that early as well?
Oliver Sartor: I like it, yeah, because you wanted to be able to find this relatively early. Within the trial, patients had to be randomized within 45 days of ADT and still have the positive PET scan. So I like to do the PET scan early and understand the distribution of disease and now you have an image-based biomarker. So we have genetic biomarkers, now we have an image-based biomarker. I want to know who's positive and who's not. And I also want to understand the distribution of the metastatic disease. Because like I said, maybe if you just have one solitary met in the iliac bone, that's maybe an SBRT patient. The ones who want to intensify are those that are going to need some help. And I'll simply say that this is a very well-tolerated therapy, and that part we know about Pluvicto from the two previous phase-three trials. And I'll simply say I think it'll be a popular therapy going forward.
Phillip Koo: That's great. So effective and well-tolerated in the right patient populations. So sort of sum things up for us. Wonderful day. I think it's wonderful when we see these expanded indications and these approvals. What are just some key takeaways for all the listeners?
Oliver Sartor: Yeah. I think the key takeaway is that we now have a method of intensification for the majority of patients who are going to present with metastatic hormone-sensitive disease, because the vast majority of these patients are going to be PSMA PET-positive. This is not something like the BRCA2 where it's maybe going to be six to 10%. It's not going to be something like the PTEN loss, which is going to be only a minority. This is going to affect the majority of your patients. I think a lot of patients are going to want this therapy. It's very popular at this point with patients for Pluvicto in the castrate-resistant setting, and I'm thinking the hormone-sensitive setting will end up having good uptake and patients are going to ask for it. So be ready for it. When it comes, I think patients are going to want it.
Phillip Koo: I got to ask one more question. So that question will probably come up. When do you deploy this great tool either in the hormone-sensitive or later? Do you wait till castration resistance? Any advice that you have for all the clinicians out there who are debating that question?
Oliver Sartor: That's a great question. And in a sense we'll have some comparative data, but it's imperfect. So the PSMAddition trial, which is the one that's positive, the phase-three that's made a difference to the FDA, does in fact have a crossover and we have a strong OS trend with the upfront treatment. I think that if the patient is eligible upfront, I'll use it then instead of waiting for the failure because at that point there are a whole variety of other things that could occur. So I'm thinking that the upfront is likely going to be the best, and now we have a strong survival trend, not just the rPFS that is indicative, and that's why the FDA has acted in a positive manner.
Phillip Koo: I think this is great news, great news for patients and gives all of the providers out there more tools to treat their patients. So another monumental day. Thank you so much, Oliver, for being one of the lead investigators and just always really pushing the envelope and bringing more choices for our patients. So thank you.
Oliver Sartor: Well, thank you, Phil. And by the way, thank you to PCF for all that you have done over the years to help make better treatments available for our patients. So PCF deserves a shout-out too.
Phillip Koo: It's our pleasure, and we couldn't do it without people like yourself, so it's a team effort. So thank you.
Oliver Sartor: Thank you.