Elisabeth Heath: Yeah, thanks for having me.
Zachary Klaassen: Let's just give a high-level background of the CAPItello-281 trial. This is the data that essentially led to the approval. Maybe just take our listeners through some of those highlights.
Elisabeth Heath: Well, I think this is in that metastatic hormone-sensitive space. This is specific to the de novo population. So, they had needed to get a biopsy of something, lymph node, bone, and really wanted to make sure that these were the PTEN loss patients, which I know we'll talk about a little bit more. And then the medication, capivasertib, is in combination with abiraterone. And then the control arm was abiraterone, so both arms with ADT.
Zachary Klaassen: Right.
Elisabeth Heath: Yeah.
Zachary Klaassen: And some of the, the rPFS benefit, talk about the side effects just so we can level set as we move forward.
Elisabeth Heath: Yeah. I mean, the actual hazard ratio is around 0.8, but if you look at the control arm, which is the ADT-Abi, it's actually much worse than it was compared to LATITUDE. So, this is sort of 25, 26 months. LATITUDE's 33 months. So, right off the bat, all of these patients were PTEN loss patients right off the bat, not behaving in a way that we had hoped for non PTEN loss patients. So, I think that's an important distinction. So, you're looking at about a seven and a half month benefit, which I think is substantial in this pretty aggressive group.
But the medication has some side effects, so I would say the top three are rash, diarrhea, and diabetes. Now, the diabetes is, for the study you could not have come on if your, let's say your hemoglobin A1C was over eight or if you were on insulin, but what they've learned, because this drug is approved in breast cancer.
Zachary Klaassen: Sure.
Elisabeth Heath: So, I think like over 6,000 women have had treatment with capivasertib, so there's a lot of lessons learned from that. So, there's just ways that we can kind of handle these side effects.
Zachary Klaassen: It's a great point. I mean, this is not new to the oncology community. We've had this drug for a while. Let's just talk about how we identify these patients, because obviously we have an approval now. This isn't for everybody. How are we going to sort of siphon out the PTEN loss patients?
Elisabeth Heath: Yeah. Many of us do genetic and genomic testing. So, I think if there's an abnormality in the actual gene and you see, oh wow, there's either a mutation or some change, I think there that's your trigger, but really it's supposed to be measured by immunohistochemistry. So, we want patients over 90% having PTEN loss. So again, that means when our pathology colleagues are looking, they actually don't see any brown staining, and I think the higher that number goes, probably the more impactful. Now, those are all sort of post-hoc looks and I'm sure we'll get information even more to that detail, but I like the fact it's immunohistochemistry. Pathologists do those kinds of tests all day long.
Zachary Klaassen: It's not a send out. They can do it right away.
Elisabeth Heath: Do it right away.
Zachary Klaassen: Yeah, I think the beauty of these discussions, we're educating hopefully our colleagues and I think this is what it's going to take to sort of get this into the community, into the academic centers, et cetera. How do you see this rolling out over the next six to 12 months?
Elisabeth Heath: Yeah. One, I think just an awareness that this is a different group of people. We're used to saying de novo versus recurrent. We're used to saying high volume, low volume. We're not used to saying, oh, BRCA. Oh, BRCA2. Oh, PTEN loss. So I think right off the bat, that's a different way to tackle the mHSPC landscape, but a good way, because this is 25% of patients are in this bucket, so that's not a small amount. I think just thinking about processing in your own practice should be, how would we really figure this out in a metastatic hormone-sensitive population? So in addition to germline testing and even if you're doing somatic testing, you may want to consider doing IHC testing right off the bat. I think they're not going to evidently look any different, but we have to be aware ourselves.
Zachary Klaassen: It's just such a call-out for, as you mentioned, genomics, whether it's PSMA signal, whether there's PTEN loss on IHC, we're really moving at a rapid pace into a precision-ish state of mHSPC. How do you sort of see this combination of Capi and Abi in the workflow as we move forward?
Elisabeth Heath: I think this is something you really do upfront if you have this PTEN loss identified. And they're kind of sneaky, because the aggressiveness of this, you don't know until you're sort of in the treatment and you realize, "Well, their PSA hasn't budged, but maybe they're having some symptoms." And then what I think you discover is those imaging studies are showing progression and your PSA did not. Now, to me as a practicing oncologist, and for you as well, that's kind of scary. We're used to seeing, "Well, the PSA's behaving, my imaging should be behaving." So that might necessitate some different follow-ups. I know what I would do, which is image more often, especially once we know this is this group. But I think as we're learning that, we're also trying to incorporate data from AMPLITUDE and are we going to offer all BRCA2 patients upfront? I think that data is also really compelling. So, it's really kind of having to redo your algorithm in your practice so that right off the bat we're offering what we need to offer.
Zachary Klaassen: Super exciting space. We're going to be able to offer our patients more precision oncology. Anything else we haven't hit on? Anything you want to leave our listeners with before we wrap up?
Elisabeth Heath: I think it's really just advocating on both sides. So, our patients need to know, but then our general group needs to know that there is a new sort of algorithm. And sometimes when we're waiting for the guideline panels to catch up, you lose time. So, this is an important finding. This is, again, a drug that is applicable to potentially 25% of patients that are newly diagnosed. So, it's really up to us to get that ball rolling in our practice sooner than later.
Zachary Klaassen: Absolutely. Well said, Elisabeth. Thanks so much for joining us, always being so generous with your time.
Elisabeth Heath: Absolutely. Thanks for having me.