Phillip Koo:

There’s always a lot of debate about who gets a doublet versus who gets a triplet. And you know there's data. But it's interesting. When you hear these debates, you could hear both sides, and even for physicians who are discussing this, I walk away, and I'm like, “there's no clear answer here, and no simple answer.” Kind of boil it down–sort of make it easy for us, you know, who in general might get a triplet, who might get a doublet?

Zachary Klaassen: 

I think in general, you know, there's this conversation we haven't touched on yet about high-volume or low-volume disease, and there's a lot of different ways to measure that, probably beyond the scope of this conversation. But in a patient, say they had their prostate removed or they had radiation. They've now ten years past that, and they've got some disease outside the prostate. That's a low-volume recurrent patient. That patient's probably going to do just fine with doublet therapy, whichever one you want to choose.

I think that as we look at deciding between the two, one–the patient has to be chemotherapy fit. What that means is that their performance status has to be adequate to undergo chemotherapy. This is six cycles of chemotherapy. This is not chemotherapy forever, or chemotherapy till the disease progresses. It's six cycles, but it's still a hard four or five months of treatment. So to be fit, you have to be active enough and have the performance status. The kidney function has to be adequate. You have to have adequate hearing. You know, the heart has to be in good shape.

All these things that medical oncology team will look at before they think about chemotherapy. I think the triplet therapy patient, especially in my practice in the Southeast, is still that young patient that shows up - PSA of 3 or 400 - that has high-volume disease. That patient we want to hit–that we want to hit that cancer as hard as we can, and we hit it three different ways. We hit it with the hormone therapy. We hit it with the darolutamide, that second-generation ARPI, and we hit it with the docetaxel.

And I think that we saw, especially at EAU and AUA, and to summarize some of that sort of post-trial data that was presented, is we want to get that PSA as low as possible as quickly as possible.  So if we're starting at 300, we don't want that PSA to go to 5. We want it to go to less than 0.2, and, in fact, Neal Shore presented at AUA, less than 0.2 even makes a difference. So the goal is hit it hard. Get that PSA down as low as possible, as quickly as possible. And that means that we're hopefully going to be able to stay on these medications and have benefit for a long time.