Phillip Koo:

We’re going to talk about the, PEACE-3 trial, which I think is really, really exciting, and sort of puts new energy into a drug that we've heard about, treating the bone. So, Zach, PEACE-3.

Zachary Klaassen:

Yeah, PEACE-3, as you mentioned, Phil, we heard about this a couple years ago, there was initial results presented, and this is an interesting population. So, you mentioned that we're still seeing some lack of treatment intensification in that metastatic, hormone-sensitive prostate cancer setting, where men are just getting ADT alone.

Which is how we did it prior to 2015, but things have changed dramatically in the last 11 or 12 years. So what's interesting of these patients is they were enrolled if they were mCRPC with bone metastases and had not received the prior ARPI. They were then randomized to enzalutamide plus Radium-223 versus enzalutamide alone. 

So enzalutamide… One of the standards of care for first-line mCRPC. The question was, could we add Radium-223? This is an injection. It's usually given 6 cycles every 4 weeks that targets specific areas in the bone. And could we improve outcomes with this combination? 

And so the answer is yes. We saw, initially, a couple years ago, this radiographic progression-free outcome was positive, and on the bottom right, we see that with continued follow-up, that still is the case.

There's a 29% reduction in progressing radiographically or dying of cancer in these patients, but it's important, now that we have overall survival data with a 24% reduction in mortality for these patients. The one thing I'll mention is it's extremely important, it's not on the slide. But if you're taking Radium-223 and enzalutamide in this setting, you have to add a bone protective agent, because what we're doing is we're treating these bone lesions with a radiopharmaceutical, which is Radium-223, plus enzalutamide can be hard on the bones, too.

We saw a significant reduction in fractures or symptomatic skeletal-related events if patients are getting a bone protective agent at the same time. So I almost think about this as triplet therapy if you think about radium and enzalutamide and that bone protective agent.

Phillip Koo:

I think that's such a great point, and I'm going to repeat it, because patients need to remember this. And I love the way you call it triplet here as well. You need to protect the bones, get the radium, and the enzalutamide. This is practice changing, so I think once the label is changed, I imagine we'll start seeing it being used very regularly in patient treatment.

Zachary Klaassen:

Yeah, I agree. This was a European trial, and I think, you know, our… I know our regulatory boards will look at it as well. It can sometimes take a little bit longer in those situations, but I agree, I think this is… we talk about practice changing versus practice informing, or early data, this is definitely something that could… could be… could be, approved here hopefully soon.