Phillip Koo:

So we're going to shift gears now to talk–a little earlier, from CRPC, so now we're going to talk about patients who are still hormone-sensitive. You know, their disease is still reacting to the hormones and being treated by it. And we heard a lot of data being presented about drugs in this space.

First off, can you talk a little bit–just boil it down for us at a simple level about what this metastatic hormone-sensitive space is, and what we learned about how we treat patients in that space.

Zachary Klaassen:

Great, great jumping off point, Phil. You know, there's sort of two buckets that metastatic hormone-sensitive prostate cancer falls into. The most common one is, people come in for a first visit, and they're diagnosed with prostate cancer that spread outside the prostate cancer.

We call that de novo metastatic hormone-sensitive prostate cancer. Roughly, about three quarters of the patients are in that bucket. Roughly, about one quarter of those patients are what we call “recurrent” or “metachronous,” another word for recurrent metastatic hormone-sensitive prostate cancer. These are patients that have had therapy to their prostate gland, whether it was removed for surgery, treated with radiation therapy, etc.

And they've now recurred, and they now have disease outside the prostate, or where the prostate used to be in other organs, such as the bone or the lymph nodes. So when we look at those patients, they all kind of grouped under this umbrella of metastatic hormone-sensitive prostate cancer, which means they have not seen ADT, such as Lupron, Orgovyx, some of the patients may be on these medicines that are listening.

And so the story of mHSPC, is what we call it, is really the last ten years has been remarkable. We started with just giving ADT. And then we had trials in 2015 and 16 that said if we add docetaxel, which is chemotherapy, to ADT, that does better than ADT alone. Fast forward another five years, sort of late 2018, 2019, we start getting these what we call “second generation androgen receptor pathway inhibitors,” such as enzalutamide, apalutamide, abiraterone, combining those with ADT did better than ADT alone. So we have what's called “the doublet therapies.”

And then fast forward another three years to about two years ago. We now have what we call “triplet therapy.” So this is combining ADT, another ARPI called darolutamide plus docetaxel, which is better than docetaxel plus ADT.

And then another study looking at ADT, docetaxel, and abiraterone did better than the ADT plus docetaxel alone. So we have gone from monotherapy, which is ADT, to doublet therapy, to triplet therapy, and really the conversation is, who's a candidate for doublet versus triplet, and that's really what we've been looking at the last couple of years. And so what was presented first at the European meeting last year was this new trial called ARANOTE. And ARANOTE is sort of the fourth study looking at that doublet of darolutamide plus ADT versus ADT alone.

And not surprisingly, it was a 46% improvement in radiographic progression-free survival. And so now we have several options in doublet. We have several options in triplet, and it's kind of figuring out who fits what profile, whether they’re chemotherapy fit, whether they should benefit from chemotherapy or not.

Phillip Koo:

You know, that was a great explanation, and I think it really, you know, shows that in patients who have metastatic disease, whether it was de novo or recurrent, whatever path it comes from, that we need to be more aggressive and sort of this idea of treating patients with more drugs actually will lead to better outcomes for those patients. What's a little concerning, though, is when you look at real world data is, you actually see how it's being implemented in the, you know, at various sites.