Phillip Koo:

Alright, we're going to move on to metastatic hormone-sensitive disease, and these genomic classifier tests, which we've heard a lot about, we've learned a lot about through these webinars, and we're already talking about some new data from Decipher.

Zachary Klaassen:

Yeah, thanks, Phil. So, Decipher is a genomic classifier, been around for a long time. I think we've talked about it several times on these events, and really exciting. It gives us an under-the-hood look at the genetics of the tumor.

And so, what we're seeing here is a big cohort of patients presented at ASCO GU in San Francisco at the end of February. And what we're seeing at the top is the M1, or the metastatic patients are in that dark red sort of color, purple color. Localized is in, in gray.

And what we're seeing is that the Decipher score, not surprisingly, with higher risk, is actually a higher score in the metastatic patients than the localized patients. So, not totally surprising, if you have metastatic disease, there's likely to be more genomic alterations that are picked up on this test. And so when we look at the bottom left, we're getting into a little bit of the nuance of this test. The metastatic patients, which is on the left, the green box is Luminal B. These are some of the bad actors in terms of the genomics. We see more in the M1 versus the localized.

So not too surprising there. What's really interesting is the pTEN inactivity. This is the middle part of that slide. We see that there's more pTEN loss in M1. Compared to localized. And this is clinically relevant because we're… we have a targeted treatment at pTEN that's currently being evaluated for FDA consideration based on a trial we've previously discussed as well. So this is, certainly very contemporary and relevant to our discussions today.

And again, not surprising, we see more pTEN loss in an M1 patient than localized. And then when we move to the very far right side, this is the very high-risk Decipher group. Again, not surprisingly, over 50% of the patients with M1 disease have a very high-risk decipher score. Compared to the localized patients. So, I think this is nice.

We always like to see big data sort of confirm what our thoughts are when we're looking at these genetic defects, and certainly the Decipher folks have done a great job of using… sort of testing their test in a number of settings, and really informing, you know, for this PAM 50 and the pTEN, as well as looking at the genomic classifier score, you know, and metastatic versus localized.

Phillip Koo:

Great, so I think this is interesting. Clearly, there's some questions about the aggressiveness of prostate cancer, how some are not aggressive, some are more aggressive. In this study, they're showing that those who have pTEN loss in the luminal B subtype are more aggressive. Obviously, there are other markers, too, that show that patients' cancer might be more aggressive.

Zach, what advice do you have for patients when they're seeing, let's say, their medical oncologist, to request this test, and how should they request it?

Zachary Klaassen:

Yeah, the genetic testing is a very… it's very… it can be very confusing, not just for patients, but even for, you know, providers, in terms of how… how we should test, what we should test. 

I'll break it down simply. We could probably talk about 30 minutes on this trial, really getting into this, but there's genomic, which is the cipher test. This is testing the tumor with a specific test. There's somatic testing, also testing the tumor.

Perhaps a different gene profile that they're looking, and then there's germline. Germline is what you're made of. This is the DNA in your body, typically with a blood or saliva test. That has implications for maybe hereditary risk, so what you can pass down onto your children. I typically tell patients.

It's okay to ask about, am I a candidate for any of these tests? I use Decipher when I'm talking about active surveillance or intermediate-risk patients. We talk about somatic and germline, typically in more higher risk patients. So ask the question.

You know, there probably is a potential at any interval of your diagnosis and prostate cancer journey, where you may be a candidate for one of these tests, is just figuring out what the right one is.

Phillip Koo:

Right, and you alluded to this earlier, I think this is exciting. pTEN, we talked about it, I believe, in the post-ASCO webinar, and hopefully we have a drug that, you know, can be used for patients with pTEN loss, again, because we know those patients have a higher, more aggressive… higher risk, more aggressive disease.

And I love the fact that the whole field is moving towards this, you know, precision, a little much more targeted, and identifying the bad actors and giving them certain regiments, and those who don't need it, they don't need to get it. So I love the sophistication that's sort of being brought to the whole field, so this is great.