A Look at Precision Medicine for Testicular Cancer Now and in the Future

Everyone touched by cancer knows treatments vary depending on the type of cancer. Now, with precision medicine for some cancers, treatments can be tailored to that cancer.

In this podcast, Dr. James Hamrick, MD, MPH, explains what precision medicine means for cancer patients and updates listeners on developments in testicular cancer treatments.

Dr. Hamrick is the chairman of the Caris Precision Oncology Alliance, known as Caris POA at Caris Life Sciences. He leads a global network of top cancer centers and research institutions dedicated to advancing precision oncology and biomarker-driven research, and he will tell us all about it.

Dr. Hamrick is board-certified in internal medicine, medical oncology, and hematology. He earned his MD and MPH in epidemiology from the University of North Carolina and completed his residency and fellowship at the University of California, San Francisco.

Now - back to precision medicine. Here's what Dr. Hamrick explains in the podcast.

00:09:55
"When we treat a cancer, it's all about hitting the cancer, the bad part, and not hurting the rest of the person. And so the more we understand the targets we should be hitting in these tumors, the better we can design treatments that hit those targets and leave the rest of the cells in a person's body alone.

"What does that mean?

"It means fewer side effects, so more effectiveness. So when you hear precision medicine, think about this: this is where my doctor is not just treating me for cancer. Not just treating me for lung cancer, but is working to understand exactly what is driving my cancer and how can we best target that so I have the best outcome, meaning we can kill those cancer cells, right?

"And the fewest side effects. That's really precision oncology. Biomarkers bio. We all know from high school biology class that the life sciences markers are the targets. So these are the targets that we can now use at Caris and other vendors. We can say, hey, that's the problem here.

"It's not just one testicular cell that went bad; it's one that has this certain molecular profile. So I tell patients: You should ask your doctors, Hey, what biomarkers do we care about? What is important? What are we targeting? What's valuable here?

"And that's part of becoming fluent in the language of your cancer, which, as many caregivers know, is really important."

Dr. Hamrick talks more about testicular cancer and the need to find genetic biomarkers for it. He explains that and related research about testicular and other types of cancer in this episode of Don't Give Up on Testicular Cancer from the Max Mallory Foundation.

Links:
Caris Precision Oncology Alliance - Caris POA
https://www.carislifesciences.com/partners/caris-precision-oncology-alliance/

James Hamrick, MD, MPH
https://www.carislifesciences.com/bio/james-hamrick-md-mph/

Max Mallory Foundation
https://www.maxmalloryfoundation.com

Don't Give Up on Testicular Cance

Transcript

A Look at Precision Medicine for Testicular Cancer Now and in the Future

Intro: [00:00:00] Welcome to Don't Give Up On Testicular Cancer, a podcast where testicular cancer survivors, caregivers, and others who have navigated the cancer journey share their stories. The podcast comes to you from the Max Mallory Foundation, a non-profit family foundation focused on educating about testicular cancer in honor and in memory of Max Mallory, who died in 2016, at the young age of 22, from testicular cancer. Had he survived, Max wanted to help young adults with cancer. This podcast helps meet that goal. Here now is your host, Joyce Lofstrom, Max's mom, and a young adult cancer [00:01:00] survivor. 

Joyce Lofstrom: Hi, this is Joyce, and with me today is Dr. James Hamrick, MD, MPH. He's the chairman of the Caris Precision Oncology Alliance, known as Caris POA at Caris Life Sciences. He leads a global network of top cancer centers and research institutions dedicated to advancing precision oncology and biomarker-driven research, which he will tell us all about. Dr. Hamrick is board-certified in internal medicine, medical oncology, and hematology. He earned his MD and MPH in epidemiology from the University of North Carolina and completed his residency and fellowship at the University of California, San Francisco.

Joyce Lofstrom: So, Dr. Hamrick, welcome. 

James Hamrick, MD, MPH: Joyce, thank you so much. It's a pleasure to be here, and obviously, this is material that is near and dear to my heart, so I'm happy to discuss it with you today. 

Joyce Lofstrom: That's great. Just tell us a little bit about your interest in oncology, hematology, and how you got going with these [00:02:00] specialties in medicine. 

James Hamrick, MD, MPH: Yeah. I think I knew from a fairly early age that I wanted to be a physician. I'm the son of a physician. And originally, I was interested in science and also in patient stories. And I thought when I started medical school that I would probably do general primary care.

And I still think that a great primary care doctor is really the best kind of doctor because they have to know something about everything. But as I proceeded along through medical school and my training, a couple of things happened. 

One, I got very interested in some of the science of blood disorders and cancers. And this was late in my medical school period, at the University of North Carolina, and then during my residency at the University of California, San Francisco. So intrigued by the science and some of the amazing advances that were being made at that time. 

This would've been, I'm dating myself, but the late 1990s, early 2000s, which it turns out was sort of the beginning of an [00:03:00] era of really understanding at a much deeper level than we ever had, what exactly is causing these tumors? What's making the cells go bad, and how can we take that understanding and lead to better treatment? So that was really fascinating. 

But still, oncology, when you're a cancer specialist, you sort of become the primary care doctor for patients with cancer. And so, deciding to specialize in blood and cancer disorders allowed me to continue to have this sort of whole-patient viewpoint, where I am kind of the primary care doctor for the patient, but also a witness to and a participant in all the amazing breakthroughs happening in oncology. 

So, I decided to pursue a HemOnc fellowship. And did that, then spent about 10 years after my training in full-time practice, then made a leap, which we can talk about, into industry, but continued to see patients up until fairly recently as well.

Joyce Lofstrom: I [00:04:00] like what you said about how the oncologist becomes like the primary care doctor in terms of taking care of patients and just knowing everything about that person. I speak from personal experience of my own, my son too. It's important for our listeners to hear that and remember that.

James Hamrick, MD, MPH: It really is important because, first of all, typically at least early in the course of treatment, you know, as the oncologist, I'm seeing the patient much more frequently than a primary care doc. I'm aware of the sort of interactions that might happen with medications, their primary care doc has them on, and treatments that I might start.

And you know this for patients and caregivers. Usually, especially in that early initial diagnosis and initial treatment and treatment planning phase, it is like a full-time job just to get to all of your appointments. It's the last thing that I want is for a patient to have to go then see a whole other set of doctors to get one [00:05:00] medication. I'll just refill your darn blood pressure medicine. 

Joyce Lofstrom: Tell us now a little bit about what you're doing with Caris Precision Oncology Alliance, what it is, and how it helps cancer patients.

James Hamrick, MD, MPH: So this is really one of the main reasons that I wound up at Caris.

Caris is a diagnostics company with an initial mission to help physicians, patients, and researchers better understand, as I said before, what's going wrong at the cellular level to cause these cancers. And the founders of Caris had the wisdom back in 2008 when they founded the company to realize that, hey, as we build out molecular testing of tumors at scale, there's going to be a lot of really potentially useful data that gets spun out as a byproduct of just doctors taking care of patients using our technology, et cetera. 

And so they realized, and no credit to James Hamrick, because I wasn't there at the time. [00:06:00] I was practicing medicine. But they realized that we should partner with the smartest investigators available to understand how to use that data. So, suddenly, we're going to know a lot about different testicular cancer patients, lung cancer patients, and breast cancer patients. We're going to understand a lot at a molecular level of what's going on.

James Hamrick, MD, MPH: If we can share that data, combine it with what we call clinical data, which, hey, what happened to this patient? What treatments did they get? How did they do? That could be really useful to investigators. And so the Precision Oncology Alliance is Caris's way of sharing that data with the smartest investigators in the field.

James Hamrick, MD, MPH: So what happens is we make it, we put it into a format that's useful. So we now have nearly half a million patients. We've sequenced close to a million patients. We take that data, de-identify it, use it to care for those patients, share it with their doctors, et cetera, and the [00:07:00] patients, to take care of them.

James Hamrick, MD, MPH: We then de-identify the data in a HIPAA-compliant manner, meaning it cannot be traced back to an individual patient. We de-identify the molecular data and combine it with the clinical data we have. On what treatments did they get? We have about half a million patients now in a data set that we can go to investigators.

We now have 99 partners at Precision Oncology Alliance, and they can write briefs, like two-page research proposals that say, Hey, I'm interested in a new question related to a biomarker in testicular cancer, lung cancer, or breast cancer. I'd like to query against your data to write up a publication.

It's been really productive. So we just crossed a pretty significant threshold: we now have over a thousand scientific publications in partnership with these investigators at many of the cancer centers everyone's heard of, helping to drive the science forward.

James Hamrick, MD, MPH: So we're really proud of that. As James Hamrick, that's what attracted me to this job: not only helping individual patients, but also helping to drive the science forward. 

Joyce Lofstrom: That's key right there. The science that you talk about. So, when I first introduced you, we talked about precision oncology, biomarker-driven research, and so forth. Tell us what that really means and how that creates a personalized approach for cancer treatment. 

James Hamrick, MD, MPH: So this era that I've practiced in, from like the late nineties up until now, there's really been a revolution, in terms of understanding what exactly, as I've mentioned a couple of times, we know this is a lung cancer, let's say, or a testicular cancer or breast cancer.

It turns out there are lots of different types of lung cancer, breast cancer, and even testicular cancer. The more we can understand the specific type of, let's say, a lung cancer that it is, the better we can tailor [00:09:00] treatments specifically to that one patient and their tumor. 

So rather than just treating, Mrs. Jones, you've got lung cancer. We're going to treat all lung cancers the same. We can get very precise in terms of understanding what is the science and what is the molecular biology that's driving that tumor? So, in lung cancer, there is a gene called EGFR, the epidermal growth factor receptor.

You don't need to remember any of that. We need to know that there's a gene that, in a certain batch, drives about 20% of non-small cell lung cancer cases. It's what we call the driver mutation. It's the mutation that's causing all this badness. The more we understand about that gene, we actually now have therapies that target those products directly.

James Hamrick, MD, MPH: And so what does that mean? When we treat a cancer, it's all about hitting the cancer, the bad part, and not hurting the rest of the person. [00:10:00] And so the more we understand about the targets that we should be hitting in these tumors, the better we can design treatments that just hit those targets and leave the rest of the cells in a person's body alone.

What does that mean? It means fewer side effects, so more effectiveness. So when you hear precision medicine, think about this: this is where my doctor is not just treating me for cancer. Not just treating me for lung cancer, but is working to understand exactly what is driving my cancer and how we can best target that so I have the best outcome, meaning we can kill those cancer cells, and the fewest side effects. 

That's really precision oncology. Biomarkers - bio. We all know from high school biology class that the life sciences markers are the targets. So these are the targets that we can now, using Caris technology and other vendors, we can say, Hey, that's the problem here.

James Hamrick, MD, MPH: It's not just one testicular cell that went bad; it's one that [00:11:00] has this certain molecular profile. So I tell patients, You should ask your doctors, Hey, what biomarkers do we care about? What is important? What are we targeting? What's valuable here?

And that's part of becoming fluent in the language of your cancer, which, as many caregivers know, is really important. 

Joyce Lofstrom: Just to know that term, what biomarkers are, that's a great piece of information to have. 

James Hamrick, MD, MPH: Yep, exactly. Yeah.

Joyce Lofstrom: So, tell me how you work with all the different medical centers and researchers that are part of finding this information. How does that work? 

James Hamrick, MD, MPH: We do a lot of work to let the investigators at all of the POA sites know. We have what we call a dashboard.

James Hamrick, MD, MPH: It's software where they can actually log in, and they can say, Hey, I'm interested in a colon cancer with this particular type of molecular profile. And we can say, good news: we've got 3,000 to 4,000 patients in our data set, all fully [00:12:00] de-identified, who you can begin asking questions about.

We have a process where they can submit an application to review the data, and then we help them with the analytics. And that very often leads to a couple of things. First of all, presentations at scientific meetings. So there are big scientific meetings where all cancer doctors come together.

There's a big one in Chicago every spring called ASCO. There are also smaller ones that focus, let's say, on genital urinary cancers or on gastrointestinal cancers. So our investigators who partner with us present at those meetings, and then, they also wind up writing a full manuscript, which we call a peer-reviewed manuscript.

What does that mean? It's a scientific paper presented in a major scientific journal that's going to be read by many, many doctors. And it's been peer-reviewed. reviewed, meaning other scientists have read it critically and said, This is valid. This isn't valid. These are the unanswered questions.

James Hamrick, MD, MPH: So we have that process whereby they [00:13:00] can write, they can do original research using our data in partnership with us, and we let them ask the questions. You know, it's not; they ask better questions than we do at Caris most of the time. In addition, we nurture communities of researchers.

James Hamrick, MD, MPH: So, because we have 99 members, there may be a couple of contracts that are closing, but between 97 and two are improving daily. Because we have so many members. What we'll do is we have different disease groups where we'll have a regular cadence of scientific calls with investigators, doctors and scientists from all these different centers who are interested, let's say in genital urinary cancers or lung cancers or breast cancer or whatever, and those doctors can get together and hear what's the research that's happening now with the Caris data and what other questions can we answer or, Hey, I'd like to be a part of that project. 

So it's a really nice collaborative community of researchers. And that's a lot of the fun of my job. We get together then in [00:14:00] person at the big meetings, we'll usually have a dinner, and then we'll hear scientific talks from members in the group.

James Hamrick, MD, MPH: And so. It's a lot of fun, and it's very collaborative as well. 

Joyce Lofstrom: Yeah, it sounds like a lot of fun, and it's also the outcomes that you're all together creating. It's just fascinating. But I've seen on your website and the Caris website a lot of different patient stories. And, recognizing HIPAA, I'm not asking for names or details about specific people. Could you give us a couple of examples of how what you're doing has helped a patient? 

James Hamrick, MD, MPH: So, a common scenario will be, we're in a moment of evolution where we, as I said, just over the course of my career, we've gone from sort of thinking, okay, lung cancer is all lung cancers, to understanding there are several different types. 

We started with things where we might test for one specific biomarker to understand, is this, for example, in breast cancer patients [00:15:00], or caregivers that have dealt with breast cancer, might be familiar with, is this "a HER2-positive breast cancer."

That's a specific biomarker. And early in my career, early two thousands, we might test for that one biomarker. Or maybe let's say in lung cancer, three to eight different biomarkers. And so we'll hear a lot about a patient who does an initial test for just one or a small panel of biomarkers.

And they're given a limited set of treatment options. And then when those treatments stop working, they'll often come, and they'll say, I want to do a more comprehensive panel. So this is where we have invested, where we are among the leaders. Our testing is very comprehensive, so we don't test just for one or two known biomarkers.

We test. All of what's called whole exome sequencing, and all you need to know about it is that it's all the DNA in our cells as humans. That actually is [00:16:00] coding, making proteins. So we test for all of that. We also test, and I'm going to push everyone on their science, memory test, all of the RNA.

Okay, so we do very broad testing. That's not just saying, let me find one or two biomarkers. Let's look at everything that might be possible. And even things that might become, there's no treatment for today, but in a year, there might be a clinical trial. So we hear a lot of stories where people say, when we got the comprehensive profiling done by Caris, we discovered a new target.

One that actually has a drug or has a clinical trial open. And in some cases. These are the happiest days at the company, and everywhere that new treatment leads to a remarkable response. That's an illustration of why we decided to go very broad early on.

James Hamrick, MD, MPH: There's a case that we have up on our website of a woman who had ovarian cancer and exhausted the standard therapies and then got Caris testing done and realized she was a candidate for immunotherapy, which is. [00:17:00] Immuno means immune system, and therapy means treatment.

There are some treatments now that everyone's probably seen TV ads for that leverage the immune system to fight cancer. And so, we hear a lot of cases like that. As an oncologist, it's remarkable to see because these were patients that even just 20 years ago, you were having a hospice conversation with, who now, some of them will go into a complete remission. So it's really gratifying and validates the work that Caris and many others are doing these days. 

Joyce Lofstrom: Well, I'm just going to share a personal story quickly. 

James Hamrick, MD, MPH: Love that. 

Joyce Lofstrom: I've had thyroid cancer. Now, four times papillary thyroid cancer, and it just came back in my lung. There's a spot in my lung, and it's a good outcome. So I went to an oncologist who basically said, Well, we don't do radioactive iodine treatment as much anymore because we can now test the tissue.

I had a biopsy. The doctor will look at different genes. He named them, but I can't remember which ones. However, this means I could have this genetic change in my cancer tissue. And there's a new medicine you can take with fewer side effects, similar to what you're talking about.

I think it's a brand new thing for me because I was like, Wow, I didn't know that. 

James Hamrick, MD, MPH: So, that's exactly it. And from a patient perspective, you know, it's how can we understand more about this particular tumor so we can find all of the possible treatments. And that happens a lot.

But it's, it's part of this being comprehensive, you know? You really don't want to leave any stone unturned because there are a lot of cases where the one thing we find. There are some very rare alterations called NTRK, and that's an abbreviation, fusions that are present in only one to 3% of certain types of [00:19:00] tumors.

But if you have one of those and have looked for it, you can have a remarkable response. We're, as oncologists, we're conservative. We rarely will say "cure," right, because it's hard to guarantee someone a cure, but a long-term remission. And we know that many of those do actually wind up being people who wind up being cured.

It's important to be comprehensive and overturn every stone. 

Joyce Lofstrom: Well, you've mentioned testicular cancer and related cancers.  Can you talk a little bit about testicular cancer? Is this an option that yes, it works.

James Hamrick, MD, MPH: So right now, we have traditional biomarkers in testicular cancer: Beta-human chorionic gonadotropin (beta-hCG), age, and Alpha-fetoprotein (AFP). Those are biomarkers, but they're not the genetic ones that we're talking about.

Testicular cancer is, at this point, still one of the ones where we're looking for the most useful biomarkers. And so we don't have, apart from those sort of traditional ones, we don't have a [00:20:00] new one that's leading to targeted therapy today. But there is a lot of investigation there. So, unlocking what the driver is in testicular cancer is a big priority.

And even though cure rates are high for some patients, there's still an unmet need in testicular cancer. There are some active areas of investigation where we're identifying molecular markers that can help us drive better outcomes for that disease. That's one of the ones tougher to crack - testicular.

Pancreatic is another one where it's hard to identify. Its cure rates are still way too low for that disease. I would say testicular cancer is an area of active investigation, and there's still an unmet need there, even though so many patients do well.

 There's still an unmet need there to drive home so that everyone benefits in this year of therapy. So as we accrue data there, this is exactly the kind of question that investigators can say, Hey, testicular cancer is my specialty. Can I, can we look at a cut of your data to ask this question or that question?

Joyce Lofstrom: Oh, [00:21:00] great. That's good to know. 

Do you think this will become, longevity-wise, the standard of care? 

James Hamrick, MD, MPH: So, absolutely molecular profiling. It is standard of care. I think where we are now is getting to where comprehensive profiling is: instead of just saying, Hey, we're just going to look at these five, or 1, 5, 10 known markers, casting a wider net and saying, actually, let's look at the entire genome. Okay, let's look at the entire transcriptome. Let's look at the entire exome. You know, those are technical terms for being broader. And it's a way of saying, there's a lot going on in these cancers at the molecular level that will help us understand how to better treat them.

Let's cast a broader net. So, to answer your question, will molecular testing become the standard of care? It already is. It already has. It's being more comprehensive. That is the next step. 

And then the other super important piece is [00:22:00] equity of access to this type of testing. So, it's moving, it's new enough, and moving fast enough that, as a general oncologist, it can be really hard to keep up with exactly what the right test is I should order, and how I get it covered by a payer.

And so making sure that everyone, not just the patients who have the means and the resources, is right. To say, Hey, I googled this, and ChatGPT did what, but everyone has access to this is a real priority. And so that's the other challenge and opportunity for the field.

Joyce Lofstrom: Okay. Wow. Yeah, lots going on. I think you probably answered my next question, what's next for you, or for your career, or anything you wanted to share? 

James Hamrick, MD, MPH: We are at the beginning of the era of unlocking what we can know about tumors and about things like cancer prevention.

We're at the beginning of that era. I'm excited to be at a company that has taken a comprehensive approach and is taking a long view because we can [00:23:00] see the potential. It's going to take time to understand, Hey, how can we not only treat cancers better, how can we increase our cure rates?

And ultimately, how can we actually begin to prevent cancers? So I'm happy to be part of that, and that's where I want to spend the remainder of my career. I would say to everyone, it's a very exciting time, or there are still unmet needs. Of course, there are, and there will be, but it's a very exciting time with the progress we're making.

Joyce Lofstrom: I think we all like to hear that cancer prevention term, to know it even works. 

James Hamrick, MD, MPH: It's becoming more of a reality. And that's exciting. 

Joyce Lofstrom: So my last question is, what song, when you hear it, do you have to sing along? 

James Hamrick, MD, MPH: No, it's a great question. I don't know if you watched. There was recently a Billy Joel documentary. They had a wonderful quote. They were talking about the song Piano Man, and they said, Well, I can tell you one thing: wherever you are, when the song Piano Man comes on, you're going to spend the next five minutes singing Piano Man. 

And that's actually [00:24:00] true. So I'm going to say Piano Man is probably my favorite sing-along song.

Joyce Lofstrom: That's a great song. It's a good one to sing to, too. I like that. 

James Hamrick, MD, MPH: That fact, it's impossible not to sing too, and everything comes.

Joyce Lofstrom: Those are words you can remember, too. Sometimes, I'm like, oh gosh, I don't know all those words. But anyway, you can remember them.

James Hamrick, MD, MPH: And they've got this great sort of every person quality, too. 

Joyce Lofstrom: Thanks so much, Dr. Hamrick, for taking the time to talk with me and my listeners. Thanks for all you're doing and, of course, what Caris is doing. It's wonderful.

James Hamrick, MD, MPH: Joyce, thank you, and thank you for speaking up for the caregivers and everything. It's a pleasure to be here.

James Hamrick, MD, MPH: So thank you. 

Joyce Lofstrom: Well, thanks. 

James Hamrick, MD, MPH: Yeah, take care. 

Joyce Lofstrom: Okay, you too.

Closing: Thank you for watching this episode of Don't Give Up on Testicular Cancer. If you enjoyed this podcast, please subscribe to our program on your favorite podcast directory. You can also visit the Max Mallory Foundation at [00:25:00] www.maxmalloryfoundation.com/podcast to listen to previous podcast episodes or donate to the foundation. Join us again next time for another episode of Don't Give Up on Testicular Cancer.