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Prostate Cancer Research: Updates From ASCO 2023

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Prostate Cancer Research: Updates From ASCO 2023 from Patient Empowerment Network on Vimeo.

Expert Dr. Channing Paller shares prostate cancer research news, including updates on the PEACE-1 and STAMPEDE clinical trials, FDA treatment approvals, PARP inhibitors, PSMA-targeted imaging, and educational resources.

Channing Paller, MD is the Director of Prostate Cancer Clinical Research at Johns Hopkins Medicine. Learn more about this Dr. Paller.

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Transcript:

Katherine:

Dr. Paller, in June, prostate cancer researchers from around the world met to discuss their findings at the annual American Society of Clinical Oncology, or ASCO meeting, in Chicago. Would you walk us through the highlights from that meeting that patients should know about? 

Dr. Paller:

Absolutely. 

We’ve had a exciting time for prostate cancer in June. So, I’d say, the first thing I would bring up is, the PEACE-1 trial was discussed again, and more data came out from that trial. That trial originally supported what we found, the STAMPEDE trial, to say, yes, we should add abiraterone (Zytiga) to androgen deprivation therapy and chemotherapy in helping de novo metastatic patients live longer and do better overall. And it also, this time around, showed us that combining abiraterone with radiation, plus or minus chemo, had patients do better. So, they had a longer progression-free survival, or metastasis-free survival. 

And also, the neat thing was, patients had fewer local symptoms in the long run. So, it prevented catheters being needed later, prevented blockages. It prevented local side effects from their cancer, which was really terrific to know, because that helps with patients’ quality of life. 

That was one of the main, personally. Go ahead. 

Katherine:

Yeah, I was just going to ask, anything else? 

Dr. Paller:

Yes. So, the second big headline, which is one of my dear loves, is all of the PARP inhibitor data. So, there were a couple trials presented, and this month has been terrific in terms of, there have been two drug approvals. So, let me talk through a couple of those. 

So, one of the big ones that was presented at ASCO was looking at talazoparib (Talzenna) and enzalutamide (Xtandi) in patients with metastatic castration-resistant prostate cancer, and it showed that the combination of those two drugs helped patients do better than enzalutamide alone, in that setting. What was also interesting is a subset of patients with DNA repair mutations did even better. 

June 20th, the FDA approved that combination for patients with metastatic castration-resistant prostate cancer with DNA repair mutations. (Lynparza) in the same space of metastatic castration-resistant prostate cancer for patients with BRCA mutations. That was a more narrow approval, but it was still very important. 

And what’s exciting here is, we’re really learning more about targeted therapy, precision medicine, for our prostate cancer patients. When I started treating prostate cancer patients back in 2005, the main drug approved was chemotherapy, docetaxel (Taxotere), and hormone deprivation therapy. And in the last almost 20 years, or 18 years, we’ve had 10 drug approvals, and we’re really starting to have multiple drugs approved based on people’s genetics.  

Katherine:

What is advanced prostate cancer? And is any of the research you mentioned focused on this stage of disease? 

Dr. Paller:

Well, advanced prostate cancer includes any prostate cancer that was extended outside the prostate, really, that’s spread to the nodes, even to the lymph nodes, to the liver, to the lungs, to the bones. And so, we have a lot of new findings, looking at this space, and that was a lot of what they showed at the ASCO conference. 

The other thing we’re learning is that we really want to get genetic testing on everybody. And so, in addition to your regular, “How do you feel?” “What do your labs show?” “What is your PSA doing?” 

We also want to get imaging, right? So, we want to look at imaging, in terms of, what did your CT and bone scan show? And nowadays, we’re moving into PSMA, or prostate-specific membrane antigen, PET scans. 

And so, that’s the new main way people look at where their prostate cancer has gone, and help them decide, what is the best treatment for me? Is it to get surgery locally, or has it advanced now, and I really need to do hormone therapy and radiation, or some other combination of systemic therapy, meaning more hormones, or more chemotherapy, with targeted therapies such as radiation? 

Katherine:

Beyond ASCO, Dr. Paller, are there other research or treatment advances that patients should know about? Anything other than what you’ve mentioned already? 

Dr. Paller:

Oh, yes. So, the other headline that I was really excited about at ASCO is watching medicine adopt the world of artificial intelligence. There was a great abstract, looking at how we can use artificial intelligence to look up pathology slides. 

So, in the past, we would always want to go to a top academic center to have your pathology reviewed by a top expert and make sure we were treating the right cancer, and make sure we really understand your risk. What we’re finding is, we can create biomarkers, and we’re understanding not just genetic, genomic biomarkers, but also pathology biomarkers, and age, and PSA, and risk, and comorbidities, and we can combine them all together and use AI to help us better stratify patients. 

And so, although it’s early, I think this is going to be an explosion in terms of helping us better define risk for patients in advanced prostate cancer, and help them figure out, do they need intensification of treatment, or can we de-intensify treatment? Can we not cause as much toxicity, and they’ll do just as well? And so, I was really excited to see that data as well. 

Katherine:

How can patients stay up to date on evolving research? 

Dr. Paller:

There are many ways to stay up to date. There are nice summaries at ASCO. There are nice summaries through the Prostate Cancer Foundation. There are good summaries at each of the institutions with whom you work. 

One of my favorite ways to stay up to date on precision medicine is one of these registries that I am co-leading, which is called the PROMISE registry. This is a wonderful opportunity which was conceived in the pandemic. 

And so, it’s pandemic friendly, and that is called the PROMISE registry. And what you can do is go to prostatecancerpromise.org and sign up if you have prostate cancer. And you say, “Hey, I have prostate cancer. This is my address. Please ship me a kit where I can do saliva testing of my genes.” And once you get your tests sent in, they’ll send you a kit, you send it back, you’ll get an email, and you can go over your results with a genetic counselor. 

And then, once you get enrolled in this program, it is really just a free information source. And so, you can learn more about the clinical trials around the country for patients with different mutations. And so, I love that as, whether or not you have a mutation and you’re going to follow with us for 20 years, because we’re going to offer you opportunities and let you be the first to know about new drug approvals, you can still hear about all of the new research. 

And I think that’s a wonderful, free resource that we’ve done for our patients to help them understand more about what’s out there. Another opportunity to learn more about prostate cancer is the prostate cancer clinical trial consortium. They have a nice website looking at germline genetics, looking at diversity, looking about clinical trial design. And so, there’s lots of different places to learn more about prostate cancer. 

An Overview of Metastatic Breast Cancer Treatment Options

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An Overview of Metastatic Breast Cancer Treatment Options from Patient Empowerment Network on Vimeo.

What metastatic breast cancer (MBC) treatment options are available? Dr. Jane Lowe Meisel provides an overview of MBC treatment approaches, including CDK4-6 inhibitors, tyrosine kinase inhibitors, PARP inhibitors, and immunotherapy.

Jane Lowe Meisel, MD is an Associate Professor of Hematology and Medical Oncology at Winship Cancer Institute at Emory University. Learn more about Dr. Meisel here.

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Transcript:

Katherine:

Right.

Well, let’s talk about treatment options for advanced disease. Can you review the types of treatments available for metastatic breast cancer?

Dr. Meisel:

Absolutely. And what I’ll do is, I’ll give you a broad overview and then because there’s so much and this is such a rich environment, I mean, I give hour long lectures just about the treatment of metastatic triple-negative breast cancer to our fellows. So, there is so much meaty information here. But I’ll give an overview with some key buzzwords so then people can go look up things that matter more to them or interest them more. So, as I said, we start with thinking about, is this hormone receptor-positive or estrogen-positive breast cancer? Is this HER2-positive or is this triple-negative? And those factors really send us down different paths.

So, if someone is estrogen-positive, I had mentioned before the PALOMA and MONALEESA studies showing that CDK4-6 inhibitors, which is a class of drugs that the first one was approved in 2015 and then two others have been approved subsequently. So, relatively new drugs. But those drugs, which are pills, added to traditional anti-estrogen therapy which would be aromatase inhibitors or fulvestrant.

Are often great first line options for these patients. And people can do well for years on just that alone, with estrogen-positive metastatic breast cancer. On average, about two years before people progress and need something new. And then after that, there are lots of trials ongoing looking at different ways in which an estrogen-positive breast cancer might progress on that regimen and how do we target that. So that there are multiple other anti-estrogen options down the line that people can use in estrogen-positive breast cancer before they need to even think about going on to something like chemotherapy.

So, really lots and lots of options for those patients, but probably starting with a CDK4-6 inhibitor plus anti-estrogen combination. And then in HER2-positive breast cancer, typically the first line treatment would be what we call monoclonal antibodies directed at HER2. So, something like Herceptin and Perjeta, which you may have heard of. And often combined with chemotherapy. But again, this is one of those areas that is also very, I think the art of medicine is very important and patient dependent.

Some of these regimen depend a little bit on patient’s age and other medical problems and desires, whether to include chemotherapy along with that frontline anti-HER2 regimen. Or whether to think about something like anti-estrogen therapy if the patient is HER2-positive and estrogen-positive. And then there are a lot of other different things we’re also using in HER2-positive disease after patients progress on that initial therapy, so there are what we call, antibody drug conjugates, where a chemotherapy like drug is attached to an antibody that then brings the chemo to the HER2-positive cell and allows for chemotherapy penetration more directly.

And then a class of drugs called tyrosine kinase inhibitors, which are oral drugs that get directed at HER2. So, another really exciting area to treat and a place where we’ve seen so many advances. And then in triple-negative breast cancer, I’d mentioned that chemotherapy has really been the mainstay of treatment historically because there weren’t great targets. But recently we’ve seen that immunotherapy, along with chemotherapy drugs like Keytruda, which you may have heard of.

Or atezolizumab, which is Mesenteric, can be used along with chemo and patients that overexpress a molecule called, PDL1. And that can actually include not just how long patients spend on the first treatment, but how long they live. So, we’re seeing a lot of triple-negative patients being great candidates for immune-based regimens now. And then for patients who have inherited a BRCA gene mutation, which many of you may have heard of. That gene mutation can actually predispose a triple-negative patient to be more receptive to a class of drugs called PARP inhibitors.

So, drugs like Olaparib or Talazoparib are new drugs that’ve been approved in the last couple of years in triple-negative metastatic breast cancer for patients who carry a BRCA1 mutation or BRCA2 mutation. And then there are also antibody drug conjugates in triple-negative breast cancer as well. The Trodelvy that’s been approved and then of course others that are in clinical trials currently. So, as you can see, it’s complex. I mean, the treatment of metastatic breast cancer is complicated. And so, it’s important I think to really be able to have a dialogue with your provider about what they’re recommending for you and why.

And I think there are often lots of options. And so, as much as you can make your doctor aware of what matters to you in terms of what side effects are you most afraid of or would you like most to avoid, what dosing schedules would be idea for your schedule for the rest of your life. So that you can deal with taking kids to school or the job that you’re currently working on or whatever, I think helps your doctor help you come up with the right regimen for you.

What Are Some Hereditary Factors Impacting Prostate Cancer Patients?

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What Are Some Hereditary Factors Impacting Prostate Cancer Patients? from Patient Empowerment Network on Vimeo.

Along with aging, hereditary factors also contribute to prostate cancer incidence. Expert Dr. Leanne Burnham details some of the hereditary factors, their mechanism of action, and some treatments under study in prostate cancer clinical trials for African American men.

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Transcript:

Dr. Leanne Burnham

So, cancer is a disease of aging, and cancer is a hereditary disease for a lot of different kinds of cancers, not all, but for a lot of them. And so prostate cancer is one of those that we know for sure that there are some genetic variations that are passed down from our parents that would make men either predisposed or not to get prostate cancer and also would predispose them to get aggressive prostate cancer.

And so, for example, if you have a father, an uncle, grandfather, if you have family members that have had prostate cancer, and beyond that, if you had women in your family that have had breast cancer, then that increases your chance as a man to get prostate cancer and to get it even younger than other races would. And so certain things that we look at in the lab and in the clinic at City of Hope are really trying to understand what those hereditary factors are, and then how you can target them with drug treatments specifically.

So, for example, we have a clinical trial that a team of us developed, and we are looking at the ability of something called PARP inhibitor not to get too technical with you, but PARP inhibitors, if you want to Google it, they are at the forefront of prostate cancer treatments right now, and especially a few running in clinical trials. And so there is a hereditary disposition, there is a mutation on the BRCA gene that leads to PARP inhibitors benefiting any person that would have that BRCA mutation.

What we’re doing in our clinical trial is we are using a PARP inhibitor called talazoparib (Talzenna), and we are not only providing that to patients that have the spark commutation, but we are extending it to patients that may not have that mutation, and the reason for is because, and I definitely don’t want to get crazy technical, but the reason for it in a nutshell, as we know in cancer there is an interaction between PARP inhibition and androgen receptor function and reaction to treatments. And so, you may have heard of androgen and androgen receptor when it comes to prostate cancer, it’s really the fancy way of saying testosterone, and prostate cancer needs testosterone, or it needs androgen and androgen receptor to function and to grow. And so, what we want to see in this clinical trial is if we target, if we use PARP inhibitors in combination with hormone therapy that’s targeting androgen production androgen receptor, will we see better treatment and better response to the drugs in those patients. And the extra cool part to me is we know that there are variations in DNA segments that affect androgen receptor function in African American men. And so, for a specific mechanism that I won’t dive into, it involves trinucleotide repeats and link, segments links and all this, but because of these variations and androgen receptor in African American men that we know was associated with their ancestry and what they’ve inherited in their own DNA, this drug should work better in African American men. And we will be able to tease that out in this clinical trial. So, it’s an opportunity for African American men who have prostate cancer who have not developed castration resistance yet, but who do have metastatic prostate cancer so, at that point, there is not a cure, right, and so you can go to your physician, and you can get a standard of care therapy, or you may want to consider this clinical trial where you would receive standard care therapy. And then also, as I said before this VIP access to this new drug, this PARP inhibitor that we think may improve outcomes in men.