Phillip Koo:

We're going to switch gears and now talk about… Which is interesting, because we've had Webinars in the past that talked about doublet therapies, triplet therapies, and now there was data presented looking at these different treatments.

In the VA population, which I think all of this stuff really helps us learn about the validity of the trials, how it actually translates into the real world, but this study from the VA, I think, was pretty informative.

Zachary Klaassen:

Yeah, no, I like this study a lot, Phil, because it doesn't tell us anything new from the trials, but it really sort of reinforces what's going on in the real world, but not just in the real world, in the VA system, where we know we have a higher proportion of minorities in the VA system, and so seeing this data presented really, sort of, was a take-home for me that how this is performing in trials actually performs in the real world in this setting is, like you mentioned, is the VA. 

And so… When we look at this, study, this was, about 300 patients each receiving triplet therapy, so this is docetaxel chemotherapy, plus ADT, plus an ARPI. This is either daralutamide, apalutamide, enzalutamide, etc., or the ARPI doublet therapy, so this is not chemotherapy, and they match them, sort of, to make them look comparable when they're doing the analysis. You can see here, median age is around 70, about 3 quarters of patients are high volume.

About 80-85% are synchronous, which means they showed up with metastatic disease. Versus having metastatic disease after initial treatment. And you can see, these are high PSAs. This is much higher than the clinical trials. The clinical trial PSAs are roughly 20 to 30. This is, around 100, so… This is what we're seeing in the real world, and I think this is important. So, the first, graph on the left shows that the patients that had a doublet, or excuse me, a triplet with docetaxel had an improved, overall survival.

What you can see here, the median has not been reached in the triplet therapy patients versus about 3 years in the doublet. And then when we look to the right, they get into some more of the nuances, so synchronous, which is showing up with metastatic disease versus metachronous, having metastatic disease later. We see a benefit for triplet and synchronous, and not a benefit to metachronous, which tells me that for the majority of metachronous patients, we may be able to consider the doublet therapy, not have to do chemotherapy.

On the bottom is looking at volume of disease, and we can get into discussion how this is defined, but the way they defined it is typically with about 4 or less bone lesions versus 4 or more. Patients with disease in the liver or the lungs are typically classified as high volume. Not surprisingly, and we've seen this in the trials as well, that the docetaxel benefit is quite important for these high-volume patients. And not surprisingly, as well as it's not as important in the low-volume patients. 

So I think… This is exactly how I think about treating my patients. It's great to see VA data in this situation, and it mirrors very similarly the clinical trials. Clinical trial patients are often… the entrance criteria is very rigid, and we often wonder how will this perform in the real world. We're seeing here exactly how it performed in the real world is how it performed in the clinical trial.

Phillip Koo:

I think that's great to see that, that, you know, that it works in the real world. I think for patients, oftentimes, they want to avoid chemotherapy. But clearly, in certain patients, in the synchronous population and high volume, there is a real significant clinical benefit. 

So, I know we all want to avoid it, but when it's indicated, you know, you should really, really consider getting that chemotherapy. And then for those who are metastatic hormone sensitive everyone needs to be on an ADT plus an ARPI, and unfortunately, there are still so many patients out there that are just getting ADT, even though they're metastatic, and we need to see that stop. And it's kind of sad that we're even talking about that today.

Zachary Klaassen:

Yeah, the one thing I'll just say quickly about that is, this is… and this, I always try to make this point with chemotherapy in this setting, it's not chemotherapy forever, it's not chemotherapy till the disease progresses, it's 6 cycles of chemotherapy, docetaxel.

Takes about 5 months to get, and then it's done. So, I think that's important when I talk to patients about, particularly these patients with the PSAs in the hundreds we start off the conversation right away at Triplet, because that's where we see the most benefit, and really, them understanding that this is a very… It's a finite time period of chemotherapy.