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Prostate Cancer Treatment Advances: What You Need to Know

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Published on January 14, 2020

All prostate cancer is not the same. Care is becoming more personalized, and new drugs and new ways of treating prostate cancer are being developed all the time. Dr. Ana Aparicio, from The University of Texas MD Anderson Cancer Center, shares news about their Prostate Cancer Moonshot research program, FDA approvals for enzalutamide (Xtandi), darolutamide (Nubeqa), apalutamide (Erleada) and what they mean for metastatic prostate cancer patients.

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Transcript | Prostate Cancer Treatment Advances: What You Need to Know

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

Andrea Hutton:         

Hello, I’m Andrea Hutton. I’m the community manager for prostate cancer for Patient Power, and I’m very excited to have here today Dr. Ana Aparicio, who is an oncologist and associate professor of oncology with the Prostate Cancer Center at MD Anderson. Dr. Aparicio, thank you so much for joining us today.

Dr. Aparicio:              

Hello, my pleasure.

Andrea Hutton:         

So, I wanted to start because I know that MD Anderson has established something they’re calling the Prostate Cancer Moon Shot. I’m wondering if you could tell us a little bit about what that is and what that might mean for patients going forward.

Dr. Aparicio:              

Absolutely. So, the Moon Shot has been an initiative that has really helped us put a program together to address the things that we feel are most important to address currently in prostate cancer. So, one of them is that we call prostate cancer one name, and yet, like many of the other malignancies, there’s actually different groups of prostate cancer. Even within people that have stage 4 or metastatic prostate cancer, not all of them behave equally.

I always put the examples of breast cancer. An ER/PR-positive breast cancer is not the same as a triple-negative breast cancer. Or leukemia, a chronic myelogenous leukemia is not the same as an acute myelogenous leukemia. And when you see people that have prostate cancer, you see those differences also, and yet, we don’t have names for them. And that really slows us down because we treat everybody like they’re all the same, and they’re not all the same. We can’t pick out the specific treatments for the specific types of prostate cancer. So, a big part of the Moon Shot is to address the types of prostate cancer that are less hormonally driven.

So, classically, prostate cancer is a disease that’s driven by testosterone—well, I shouldn’t say testosterone. It’s driven by the androgen receptor. And so, most of our drugs are going to in some way block the activity of this androgen receptor. And that’s sort of your more common garden variety of prostate cancer, but there’s a subset that we think is about 20-30% of the group that does not seem to depend that much on that androgen receptor activity, and we don’t really have good treatments for that subset. And so, that’s a big effort. We’ve called them the aggressive variant prostate cancers, and that’s a big effort of the Moon Shot. 

And then, the other big effort of the Moon Shot is to get to better understand the tumor immune and non-immune micro-environments of prostate cancer, and, more importantly, how can we modulate that micro-environment to help treat it in a better and more durable way. You may know that the immunotherapies thus far that have been pretty successful in other tumor types have not been that successful in prostate cancers. So, why is that? Clearly, we need to harness that immune system to help us treat the disease as well. 

Andrea Hutton:         

So, when you say tumor micro-environment, what does that mean? Is that inside the tumor? Is that inside my body? What does that mean?

Dr. Aparicio:              

So, the tumor micro-environment is, if you think of a garden—not that cancer is necessarily pretty, but the flowers are the cancer cells, but you have grass, you have weeds, you have the soil, you have roots, you have bugs. It’s everything else that’s surrounded those cells. So, the cancer cells don’t live in isolation; the cancer cells form tumor masses, and these tumors need to be fed by blood vessels. They need to have a structure on which they live, to which they’re attached. There are immune cells that come in, or don’t in enough numbers. So, that’s what’s called a tumor micro-environment. There’s the cancer cell and everything that surrounds the cancer cell. 

Andrea Hutton:         

I’m a breast cancer patient, and I know in breast cancer we talk a lot about the different drivers of the tumor, like you said, ER-positive and triple-negative and those kinds of things. So, what I’m hearing—is this correct—what you guys are working on is trying to establish some of the markers for prostate cancer in a way that hasn’t been done before?

Dr. Aparicio:              

Right, because in distinction to breast cancer, the staining for the androgen receptor doesn’t necessarily predict the response to an androgen receptor directed therapy. So, there’s that difference. So, just by staining for the androgen receptor, that marker’s not good enough to tell us what to do next.

Andrea Hutton:         

It sounds like an amazing sort of incubator and brainstorming opportunity. 

Dr. Aparicio:              

It is. It’s been wonderful. 

Andrea Hutton:         

Wonderful. I also was reading that there is a new drug that was recently approved by the FDA for prostate cancer. Can you tell me what it is and when people can expect to see that change in the clinic, or what patients might want to know about it? 

Dr. Aparicio:              

So, the drug itself is not new; it’s the setting in which it’s been approved is new. Again, the androgen receptor is the engine of many prostate cancers, and so through the years we’ve had a number of drugs that blocked this androgen receptor. So, the very first one was called—it’s all the -utamides. So, the very first one was called flutamide, then there was bicalutamide (Casodex), nilutamide (Nilandron). Then there was enzalutamide (Xtandi). Now there’s also apalutamide (Xofigo) and darolutamide (Nubeqa).

What this approval is based on: we used to use at least enzalutamide and apalutamide. We used to use it in the hormone resistance setting, so once the prostate cancers had developed resistance to the withdrawal—so, the first line of treatment is the withdrawal of testosterone from the cancer, and that produces a response in 80 percent of people. But then the androgen receptor still figures out a way to keep driving that disease, and these AR-targeted agents such as, enzalutamide, block that androgen receptor. It was approved several years ago to be used once those prostate cancers were resistant to just the withdrawal of testosterone.

And what this indication is for now is that our clinical trials have found that if you bring in and withdraw the testosterone and at the same time you block that androgen receptor, people do better than if you do just the withdrawal of the testosterone alone. But that’s in line with a number of clinical trials that have shown that the combination of drugs that we used to use later on in the disease course, earlier on with just the testosterone withdrawal, makes a difference. In the same space, you have docetaxel, which is a chemotherapy. You have enzalutamide, which just got FDA approval for this indication. Again, it was approved pre-receipt. Abiraterone, which is also works on withdrawing androgens from the cancer, and there’s also apalutamide. So, those are the four that currently give that indication.

Andrea Hutton:         

How many drugs are now possibly being used in combination? So, is it just one plus one, or in early settings are there going to be multiple?

Dr. Aparicio:              

So, right now, as it stands, it’s just one plus one in most settings at most. There have been numerous clinical trials that have looked at combinations that actually looked really promising, and then in the large three-phase clinical trials, that vantage was not observed. And we think a large part of it is this dilution of the phenotypes, right?

Just think about it, if you put all of the—there’s this one drug that’s great for ER/PR-positive breast cancers, but doesn’t work in the rest, but you still put all the breast cancers in that same clinical trial. Then teasing out that effect and that efficacy is very hard to do. And I think that’s been a limitation in our clinical trials, and that’s why we’re so invested in trying to put class at least in buckets. We can then refine those buckets, the same as in triple-negative breast cancers are not all the same; some have certain features and respond to certain drugs, but at least you have three buckets that you can start being a little more specific about.

Andrea Hutton:         

What we keep hearing about in so many cancer settings about precision-targeted medicine, so it sounds like this is exactly that, where trying to understand what the targets really are better for prostate cancer and then applying the precise drugs for the drivers of those specifics. 

Dr. Aparicio:              

You’re absolutely right, and there’s actually been a big effort recently where people have found that mutations in genes that are involved in DNA repair predict for a higher response to a certain class of drugs, the PARP inhibitors. So, that’s been very exciting. So, that’s along the lines of precision medicine. We’re trying to approach it from a different perspective. For us, it’s not about drug development; it’s more about therapy development.

So, just having a response rate to a certain drug isn’t enough. There’s a lot of discussion, for example, about whether or not we should be treating the primary tumor in the setting of metastatic disease. So, if somebody walks in and their disease is already outside of their prostate, should we be treating that prostate tumor or not? We haven’t done it, but now maybe is a time we should. And our view is that answer is not going to be the same for all three buckets of disease, if you will. So, that’s why we’re trying to define it more—I think it’s a more comprehensive definition, rather than specifically one gene and one drug, if that makes sense. 

Andrea Hutton:         

Yeah, a very exciting new approach to thinking about how to treat the disease. And I know you see patients as well. You’re thinking about research and the future, but you’re also seeing patients on a daily basis. So, if there are your top three things maybe that you would like patients to know in the prostate cancer community, about either what’s happening right now with treatment or what’s happening in the future. Even with the idea of combinations, how might that affect the side effects of the patient experience when we start putting more things together? What do you want individuals to know?

Dr. Aparicio:              

So, there are a couple of things: One, I think that we’re making advances and that there are some very promising clinical trials going on right now. And I would urge everyone that if they can—this is often not easy or possible—to consider participating in a clinical trial. Because I think that’s also a big limitation in prostate cancer: many people won’t, and that slows us down.

Andrea Hutton:         

And it’s important to know that participating in a clinical trial means that you always get the standard of care. So, it’s not like you’re only going to get a placebo and not be treated. You’ll always get whatever the normal course of treatment might be, and the question is whether you might have something added onto that or not.

Dr. Aparicio:              

Right, exactly, so that’s one view. And then the other view is it gives you one more option in terms of a new drug or a new target. It’s a big commitment, but if one can, that’s a big piece of it.

The other thing is that a lot of times people think of chemotherapy in the course of prostate cancer as a last resort. It’s not. You have x number of drugs that are available for the treatment of prostate cancer, and it’s not about if, it’s about when. And bringing in chemotherapy earlier—in fact, there was just a clinical trial that showed—the hormone treatments are generally pills, and so they’re more acceptable, but there was just a clinical trial that showed if you did the chemotherapy before you did a hormonal—if you sequenced it in that way, people did better. What matters is, at the end of the day you should be going through most of these drugs because they’re available. 

A lot of people that we sit in the clinic and they say, “Oh my God, you’re saying chemotherapy, and it’s so early, and I thought I was going so well.” We have them and it’s like, “No, you’re fine. I think this a good time to use this chemotherapy.” And the same for clinical trials: this is a good time to consider a clinical trial, and then we have all the rest of our drugs that we can use (which are many) for prostate cancer.

Andrea Hutton:         

Well, that’s a very important piece of information. So, thank you so much for bringing your knowledge and hope to our prostate cancer community and for your time. So, thank you so much.

Dr. Aparicio:              

My pleasure. Thank you.

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

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