Neal Shore: My pleasure, Pedro. It was great seeing you at AUA as well as at ASCO.
Pedro Barata: So Neal, today we'll be talking a little bit about one of the amazing efforts you help leading, which is this precision data platform study where you basically, if I got it right, you basically gather very important data in over 20,000 patients diagnosed with metastatic hormone-sensitive disease, the new nomenclature, androgen modulation pathway sensitive or naive over roughly a period ofa four years or so around community urology practices. So I guess I will start from the beginning. What triggered you to put together such a database and what you had in mind when you put it together? And by the way, how do you made it happen? Because this is one of the largest database that I'm aware of.
Neal Shore: Yeah. Well, thanks very much, Pedro. Like everything, this was a collective group effort sponsored by the research arm of Novartis and they came and they really put together a wonderful group of multidisciplinary collaborators; urologists, medical oncologists, myself, Elisabeth Heath, Dan George, Oliver Sartor, Xiao Wei. And then they have this amazing group of investigators within Novartis, Jennifer Nguyen, Jeetvan Patel, Mark Fallick, Barinder Kang, Clare Byrne and Chris Lavallee. We together for the last several years have been working through the PPS data analytics precision data platform. And it's over 80,000 patients with a confirmed diagnosis of prostate cancer over a 10-year period.
I think one of the things that we recognized was that things have changed a lot in that 10-year period where we finished up looking at towards the end of 2024. And what we were looking at, and we call this PRECISION, it's an acronym for Prostate Cancer Disease Observation Data Platform Analysis. So we picked those selective letters and come up with PRECISION, but it's really been a treasure trove of great data. So one of the things that we were particularly interested here was looking at the key points when somebody was diagnosed in a community urology practice, because this is all electronic health records and claims data from that PPS setting. And so this is real-world data.
And what we looked at was the diagnosis as the index date of prostate cancer, index dates for developing resistant disease. We looked at when patients were referred by the urologist to a medical oncologist, whether they had sensitive biology or resistant biology. And then we looked at the patterns of when they got referred and what types of therapies they received when they had either sensitive or resistant biology. And it was a big undertaking and a big analysis. And as you can imagine, it's real world, so there's always some limitations to that.
So it was essentially, again, to say this concisely, we had the index dates, sensitive biology, resistant biology and what was some of the percentage of pre-referral and then later on referral with resistant disease. I'll just sort of jump to the conclusions because it's busy and I think the readers can see this poster is really kind of jam packed. I generally try not to make these posters so jam packed, but this was just such a chock-full of great, really fascinating information.
But the bottom line, when we look at our conclusions was that with expanding treatment options in metastatic disease, the referrals from the urology community practices really decreased significantly to the oncology practices. But when the urology practice ... Because they started doing the orals is basically it and they started getting comfortable with the ARPIs. But when the urology practices, this is all US based, would refer to the medical oncologist, we'd start to see an increase in RLT, we'd see an increase in PARP inhibitor use, we'd see an increase in taxane use. And so this was really quite a profound notion.
Yes, the uro-oncologists were holding onto these patients increasing their ARPI use, still some monotherapy, ADT, which we all know is no longer really the standard of care. So we see these decreases, but when we see the referrals, the patients are getting more life-prolonging lines of therapy. And one of the takeaways is just really hammering home, at least in my mind, the importance of multidisciplinary collaboration. And as we go more and more, as we're going to publish this, we try to see these gaps in the patterns of referral. What are some of the strategies that we can do to improve multidisciplinary coordination?
I was really, really happy that we won the best poster award at AUA for this year for this particular poster and Jennifer Nguyen presented it with me. She did all the hard work of going through all the data. I just kind of stood there and admired her great presentation and answered a few questions. So really kudos to her. Anyway, but all the other folks that I mentioned, these are really important because we even see different trends from the first five years of the 10-year sweep to the most recent five years. And I think you and I have been on so many things together where we're really pushing the importance of more biomarker genetic testing and more and more collaboration. So I think that looking at this data and seeing some of the changes and how it impacts ultimately patient care is what's really the most important.
Pedro Barata: Well, Neal, beautiful summary. And when I was looking at that, again, I was kind of looking at what you just described, the pace of the utilization of therapies beyond ADT. We tend to call them treatment intensification and you see that over time getting better and it's important to see it. And to your point, I mean, it does reflect, I guess, the efforts out there by you and many folks involved in raising awareness, educating, et cetera. So I see one of the benefits, an obvious benefit is to understand where we are and try to understand how the different practices are adapting to it.
So I guess as I look forward, the question that I have for you is with so much biomarker-based therapies, whether there's PSMA-based therapy, whether it's genomics-based interventions, how do you think this database will look like when you start getting a deep dive into, for instance, patients tested with genetic testing, germline and somatic use of biomarker-based therapies like PARP inhibitors or even immunotherapy? How do you think this unique urologic database, what do you think we're going to be seeing, or you're already looking at that and you can share something with us?
Neal Shore: Yeah, it's such an important question. Look, when you compare the use of taxanes, for example, in the US versus I think outside the US, there's a lot more use of taxanes. I mean, I personally have used a lot of taxanes and I've been using them since 2007. I think there's still some under utilization potentially in the urologic community by not having greater integration with our medical oncology colleagues for certain types of patients with liver metastases or large volume painful bony metastases. And of course they have to be chemo taxane eligible, taxane fit.
But then also just the awareness for our patients with metastatic disease who should be ubiquitously getting somatic testing, looking for specific alterations on the homologous recombination repair side of things, even the occasional but less common TMB high, MSI high. Now we start to see patients who may benefit from finding certain types of immunohistochemistry issues such as PTEN, even HER2.
So I think to your point, and your question is such a good one because not everybody is comfortable working in a multidisciplinary way with their pathologist to do the appropriate testing, to make sure that they can get it. There's always the germline consideration for helping other family members recognize their risks of having HRR most commonly recognized would be the BRCA2. But I think this type of data and the efforts of you and myself and many others is to try to get that more accessible now for patients.
A lot of folks are doing the PSMA PETs, which is really fantastic because that's a great imaging biomarker for radioligand therapy and particularly lutetium-177-PSMA-617 and where we have approvals already right now in both pre and post chemo resistant biology, it may come because of the ADDITION trial (PSMAddition trial). We may also see that in mHSPC. So we don't use a lot of triplet right now with taxane, but we may start to use a lot more triplet with radioligand therapy for our mHSPC patients who are now more appropriately APMN/APMS and even PARP inhibitors, triplets with an ARPI and a PARP inhibitor and ADT. We'll see if we may get an approval for IHC PTEN loss and the AKT pathway on capivasertib. That's another triplet.
So what I think is super exciting, Pedro, is the fact that urologists working hand in glove with the medical oncologist, whether it's community or academic, their nuke med, their radiation oncologist, so that we can really ultimately, as you said, optimize patient care, maybe make it more intense upfront, maybe have an opportunity to de-intensify later.
Pedro Barata: Right. No, that's wonderful. I mean, congratulations on the award and that's probably the reflection of the understanding of the society, that indeed that multidisciplinary collaboration is really needed. So we really welcome data sets like yours, you and many other colleagues are helping put together. It's really a large effort. Again, congrats for that, Neal. And of course we look forward to read the manuscript and also to cite it a lot because that kind of gives us the lay of the land, I guess, where are we and what can we do to improve upon where we are right now? So from that perspective, the landscape is changing so rapidly that having a picture of where we are each time is tremendously important.
Neal, always a pleasure to get you on and get your insights on this. Again, congratulations. So nice to chat with you and we're probably going to be here very soon with your paper out to talk more about those details. Thank you.
Neal Shore: Thanks, Pedro.