Capivasertib for Prostate Cancer: What Patients Need to Know
Dr. Zachary Klaassen of Wellstar MCG Health and Dr. Elisabeth Heath of the Mayo Clinic discuss the new approval of capivasertib (brand name: Truqap®) for certain men with metastatic androgen pathway modulation-naïve or sensitive (mAPMN/S) prostate cancer whose tumors have little or no PTEN protein. This tumor characteristic, called PTEN deficiency, can make prostate cancer grow faster and respond poorly to standard treatments.
Note: mAPMN/S is a newer term for metastatic hormone-sensitive prostate cancer (mHSPC).
Transcript:
Zachary Klaassen, MD, MSc [00:00:00] Hi, my name is Zach Klaassen. I’m a urologic oncologist in Augusta, Georgia, and I’m excited to be joined on the Prostate Cancer Foundation recording with Dr. Elisabeth Heath, who is a medical oncologist at the Mayo Clinic in Rochester, Minnesota. Today, we’re gonna be talking about a new indication, a new treatment for metastatic hormone-sensitive prostate cancer called capivasertib. Elisabeth, thanks for joining us and discussing this so our patients understand exactly what this new drug is.
Elisabeth Heath, MD, FACP [00:00:25] Thanks for having me.
Zachary Klaassen, MD, MSc [00:00:26] So let’s start at the top. What is metastatic hormone-sensitive prostate cancer, and what is this new medication, capivasertib?
Elisabeth Heath, MD, FACP [00:00:33] Metastatic hormone-sensitive prostate cancer is when right at presentation, whether you’ve had prostate cancer before or literally you’ve never had prostate cancer, you then have spread disease right off the bat. So that can mean cancer in the bones, cancer in the lymph nodes. Actually, once you get to the lymph nodes, you’re already a stage four out of four. So that tends to be an eye opener of a statement for many of our patients. But we call it hormone-sensitive because the front line of defense there is to get rid of that testosterone that many men are very fond of and don’t want to get rid of, but when we do that, we control the cancer. And so that’s a really important finding. Now, whether it’s CAPI or capivasertib, maybe, you know, be lots of different ways to pronounce it, but it is a new type of drug. It’s called a PI3 kinase AKT inhibitor. So just a whole different way to try to kill the cell.
Zachary Klaassen, MD, MSc [00:01:33] It’s basically targeting a different sort of pathway than we have in the past.
Elisabeth Heath, MD, FACP [00:01:37] It is, and it’s kind of a, not just annoying, but it’s a nastier, more aggressive pathway. We’re here beating up that androgen receptor all day, every day, and get rid of that testosterone, maintaining it, but when you don’t have PTEN, which is a pivotal part where that PI3 kinase doesn’t go to AKT and then wreak havoc a different way on that androgen receptor sort of environment. It’s got sort of no breaks. So, this drug kind of reinstates that and says, well, wait a second now, let’s gain some control here. So, you kind of need both is what we’re learning.
Zachary Klaassen, MD, MSc [00:02:16] And this is, it’s a great explanation, it’s just what we’re talking about and what we are going to discuss about this new indication. This PTEN deficiency, just explain for our patients and their caregivers what that is.
Elisabeth Heath, MD, FACP [00:02:26] That sort of gene and or now protein, not to have a biology lesson, but it’s sometimes in a lot of what we do, it isn’t always about the DNA, right? So, we’ve talked a lot, especially in many, many conversations about, well, I have a gene that doesn’t work right, like the breast cancer gene. I think we’ve gotten some pretty good education around that. This is the PTEN gene, but it is more than the gene. Now it’s what does the gene spit out. In this case. It’s the protein. So, what we don’t want is, you know, to just look at the gene as sort of the sole way to see what the problem is. So, we’re actually calling this state when you’re looking as a PTEN loss status. So that’s how we know.
Zachary Klaassen, MD, MSc [00:03:13] Great explanation. Why is there an unmet need for these specific PTEN deficient tumors or patients? We had this big trial that led to this approval. Why is an unmet need here?
Elisabeth Heath, MD, FACP [00:03:24] This group that’s sort of driven by you know, this concept of, again, PTEN loss, or just you don’t have it working right, aggressive, very aggressive. And they’re aggressive in a way that we can’t tell. So, in most patients, we get that number down, PSA goes down, and it stays down. And you know on occasion, you might do some imaging in the sensitive space. Most of the time you don’t until that PSA sort of creeps back up and then you do it and then say, oh boy, there’s some new areas. PTEN loss patients don’t have that luxury. Sometimes we’ll see progression on a scan, their PSA didn’t budge. So, the way it’s really revving up the cancer doesn’t work in that traditional way that we’re used to. So that is a, you know, it’s a really tricky way of it showing its aggressiveness where it’s not allowing us in our traditional ways of measurement that things aren’t going right. We just don’t know. But knowing that they’re this, you know, might prompt you to image more and be on the lookout much more closely than you would if you didn’t have this PTEN loss.
Zachary Klaassen, MD, MSc [00:04:31] That’s a great lead into my next question. How do patients know if they are candidate for this new treatment?
Elisabeth Heath, MD, FACP [00:04:37] It’s again, back to that protein. So, we do a lot of genetic and genomic testing. You and I’ve had multiple discussions, standard of care, inherited panel. But in this case, it’s actually a test done by the pathologist known as immunohistochemistry. That is your old school way of figuring out on a stain. So, you know, whatever is the biopsy you put it underneath the microscope after the pathologists look for a particular stain. And actually, what you’re looking for is an absence of that stain. So, the more absent that stain is, the more it’s going to not do well and the more it will respond to this new agent.
Zachary Klaassen, MD, MSc [00:05:15] And this is an important point, I think, because any pathologist can do this stain, right? This is not some fancy biomarker that we have to send off for special testing. The pathologist is looking at the tumor. They can run this test.
Elisabeth Heath, MD, FACP [00:05:26] Yeah, and pathologists are often doing multiples of these. So, for example, what do they do in a lot of places? They check PSA. So that’s the protein that they’re testing. And most of them will turn brown on the slide and be like, oh, there’s the PSA protein. Here we’re looking again for the opposite. Yep, we’re looking at the stain. Oh, you don’t have a stain. That’s actually more worrisome. But they’re used to this. They do it for not just prostate cancer, they do it for all types of cancers. So, it’s quite routine for a pathology.
Zachary Klaassen, MD, MSc [00:05:56] Can you just give a general idea, something gets approved by the FDA, how long does it take to get into practice as insurance covers it, this is tricky, but maybe just a high level for our patients and their families.
Elisabeth Heath, MD, FACP [00:06:07] Yeah, I think it’s still going to take some time, right? So there has to be this processing and then there has to be the education piece as well. And then also a recognition of, you know, who are the right patients. So, if you understand, well, I’ve got to check this, I got to check that it’s still a new workflow for a lot of people. So, I think as we sort of proceed, it’s really important that the patient himself will understand this is a new process and anything that requires an extra step, it’s always a learning curve, but it’s a pretty straightforward extra test. So, it shouldn’t really be a huge learning curve.
Zachary Klaassen, MD, MSc [00:06:45] You know, I think many patients listening to us might have a urologist that they’re seeing. Maybe they’ve met a medical oncologist like yourself. Who do you think’s gonna give this treatment once it sort of rolls out and we’ve got the workflow as you mentioned?
Elisabeth Heath, MD, FACP [00:06:58] You know, there are some side effects to this medicine. So, you have to be really on top of how to manage. Most of the urologists I collaborate with will defer to medical oncology to manage these kinds of issues. I think in general, at least in the United States, most will probably be, you know, getting this medication from medical oncology, but there are plenty of skilled urologist who have an advanced prostate cancer clinic and a practice. And so, they feel confident and have, you know the infrastructure and just have either the nursing help or expertise with their NP or PA, then that’s okay too. So, it is a pill. This much is like who prescribes PARP inhibitors. Not everybody does, but there’s sort of a pattern that people fall into that they’re comfortable with.
Zachary Klaassen, MD, MSc [00:07:46] That’s great. Final question, just some advice for our patients, maybe a take home message. When should they be asking about this? How should they, you know, knowledge is power for our patient, so how should they discussing this with their clinicians?
Elisabeth Heath, MD, FACP [00:07:58] I think if you are a metastatic hormone sensitive patient, just like we chatted about earlier, the first question is, am I eligible for this medication? Because now we’re getting into the weeds in a good way, where before it was, well, it was everybody treated the same. Then it was oh, we have many options, which is really great, but they’re still all sort of the right answer. And then with this change in the BRCA2 patients, it’s now getting a little bit more nuanced now. With PTEN loss, it’s even more nuanced. So, it’s not up to the patient to know, it’s really up to patient to ask and advocate as well, just so that the conversations can be two ways.
Zachary Klaassen, MD, MSc [00:08:38] Well said, Elisabeth. Thanks so much for joining us on PCF.
Elisabeth Heath, MD, FACP [00:08:41] Absolutely. Thank you so much.