Phillip Koo:

Great. Alright, so we're going to go to the last area of survivorship, and we've talked about this, we've talked about ADT and how there are side effects, and cardiovascular events are something significant, so there's some data presented at GU ASCO on cardiovascular events in ADT.

Zachary Klaassen:

Yeah, I know, Becky, mentioned off the top that one of my interests is survivorship, and this sort of falls in that line. I think the reason survivorship's important, I'm just gonna take a step back, is we know that roughly there's gonna be… the prevalence of prostate cancer, people living with prostate cancer, is about 3 million people in the United States. We know that about 35,000 a year will pass, unfortunately, from prostate cancer.

But survivorship's important because most men will live with prostate cancer and likely pass from something else. And that's something else, oftentimes, is cardiovascular issues.

We know that cardiovascular disease is the number one cause of mortality in the United States, and it's very high for men that have prostate cancer. Part of that is just being a male in this country and those risk factors that are inherent. But also, a lot of the treatments that we give increase the risk of cardiovascular disease, so I spent a lot of time on… on discussing that and making sure they're either plugged in with their primary care provider, or even better, a cardiologist.

We have a cardio-oncologist at our institution that we use very liberally, particularly in people that are starting some of these treatments, have risk factors that are going to be on, you know, ADT. We've talked about enzalutamide, we've talked about chemo. All this can increase the risk of cardiovascular disease.

This study looked at… it was a… it was a claims database, so big numbers. As you can see here, they were sort of divided into agonist, initiators. This is commonly your Luprons, your Leuprolides, and antagonists, and then… and the antagonist initiators.

Which is commonly your Degarelix, your Orgovyx, and then looking at baseline cardiovascular disease versus no baseline cardiovascular disease. So what this study showed us on the right, that the two-point MACE was a scoring system that they looked at either heart attack or non-fatal stroke, the 3-point MACE was those two, plus any other cause of mortality. So that's why there's the two metrics that they looked at.

What this tells me is on the top, overall, rates of change in 2-point or 3-point MACE per 100 patient years. The highest risk is in those with baseline cardiovascular disease. So this is not surprising. If you have predisposed conditions, that's gonna be your biggest risk of having a MACE event once you've started therapy.

What's interesting, too, is that if you look at the antagonist versus the antagonist and the Relugolix initiators, we know that the antagonists likely have a less cardiotoxic effect. We're seeing that in this real claims-based study. And then if we look at the bottom.

Again, this is change in the prevalence, before and after Relugolix approval. Relugolix is the oral pill, the antagonist, and we see, again, the biggest benefit is in those with a baseline cardiovascular disease. And so the take-home for me in this is, is it's super important to know your risk factors going into starting treatment. And so, that may be, again, partnering with your primary care provider.

Making sure you're on a statin if you need to be, making sure your blood pressure's controlled, making sure you're not smoking, making sure you're exercising, eating a heart-healthy diet. I send men to the American Heart Association website, and I usually give it to their family members, because they're the ones paying the most attention to these sorts of things, too.

And really helping them follow that, because at the end of the day, we want to treat their prostate cancer, we don't want them to die of prostate cancer, but we know the elephant in the room is the cardiovascular disease.

Phillip Koo:

Great. That's, very helpful, very interesting. Cardiovascular disease and those side effects are real significant.

Tell us… give us some counsel on the antagonist versus agonist. The way you present it, does this mean everyone should be on an antagonist, not an agonist?

Zachary Klaassen:

Yeah, it's an interesting debate, Phil. I don't know if I have a perfect answer for you. I think that there's some aspect of the antagonist injection is typically every month.

The antagonist pill is obviously a daily pill. The Lupron or the Luprolide is typically every 3 months. Some of it's convenience if somebody's driving 4 or 5 hours away. I think the way I look at it is that most people will be just fine on an agonist, such as a Lupron injection, but we do have those patients that have a cardiovascular risk factor, or 2 or 3.

And those are the ones that we probably need to… to push insurance companies for coverage for Relugolix, or getting them on that monthly, injection that's the antagonist, because I think that's… we're seeing more data, and we're seeing it in this study, that they have less cardiovascular risk with that treatment.