Care Partners Compass: Navigating CRC

Biomarkers and CRC
Elsa Lankford

Elsa 0:00
Welcome to Care Partners Compass Navigating CRC. My name is Elsa Lankford. I am the care partner to my incredible wife, Kristine, who has stage four colorectal cancer.

In today's episode and in a few of the episodes, I am joined by my friend Annie Delores. She's been a patient advocate for CRC for almost seven years. She's very involved in colorectal cancer and KRAS social media groups and communities. She selflessly shares her wisdom and research at conferences and online.

Elsa Narration 1:08
Before I do an episode on the second kind of chemo that Kristine did. It's important to talk about biomarkers, what they are and why they're important. Cancer is essentially a series of genetic changes that allow some cells to keep growing and multiplying. These changes can be from a combination of errors, damage,and they can be inherited

------ Very basics of biomarkers ------ 1:30

Elsa Narration 1:30
Biomarkers are the combination of mutations in the tumor. There can be many different combinations of biomarkers, even for people with the same kind of cancer. There can be variations. Some chemo immunotherapy or clinical trials are available only for particular biomarkers. That's why you want to know your loved one's biomarkers to understand the options At Kristine's diagnosis I thought cancer was cancer, just like the human body. Cancer is incredibly complex. not only are the different kinds of cancers unique, but two people with colon cancer, the same age, gender, ev the same. They can have incredibly different biomarkers. The tumor will have its own set of mutations and then there can be person specific inherited mutations as well. Those get passed down from your family and could be passed down from you to your family. This episode is going to get a little sciencey as Annie stops by again to be a guest on the podcast as she is a true expert in certain biomarkers. As you'll hear in this episode. It took me a while to know what Kristine's were, and that was fine. This is a journey

------ HER2 (ERBB2) mutation ------ 2:44

Elsa Narration 2:43
where your brain needs to be ready for all of the information and all of everything. if learning scientific information is not for you, then hopefully you can find somebody to add to the care partners circle that will help you be able to do some research. There's going to be another episode, probably more than one episode, about some ways to get started researching.

------ Background on CRC ------ 3:12

Elsa Narration 3:12
I did want to do a little background on CRC There are three categories of how people get colorectal cancer. The first is called sporadic. That means there's not a family history of that cancer or an inherited DNA gene mutation that would increase the risk. Sporadic is 50 to 60% of CRC cases. Familial happens 30 to 40% of the time. And what that means is that somebody in your family had or has colorectal cancer, which makes you more likely to get it. their family members should be screened ten years before the age of diagnosis. hereditary is 4 to 6%. most of us know when we hear about BRCA genes that we think about certain cancers like breast cancer, scientists and researchers are starting to get a better sense of these mutations that increase the risk of CRC for people.

------ Main CRC biomarkers ------ 4:10

Elsa 4:10
let's talk about some of the main biomarkers in CRC.

Annie 4:14
Yeah, so almost 50% of colorectal cancer has either a KRAS mutation, which is about 45% of all CRC patients, or an NRAS mutation, which I guess is about 2 to 4%, And then there's a BRAF mutation which is about 8 to 10%. There's a HER2 mutation amplification, which is about 2 to 4%. It's more common in rectal cancer patients like one out of seven rectal cancer patients have a HER2 mutation and then there's fusion like NTRK. So when you take all of those away, you have about 40 who are KRAS wild, which means they have no mutation BRAF wild NRAS wild. And so they have the option in a their first or second line if they're stage four of having an EGFR inhibitor such as Cetuximab panitumimab, and they even have the option of RE challenging it down the road it looks like they might still get additional benefit for trying it again.

Elsa Narration 5:21
I'm going to hit pause here for one second because in the first edit I did on this podcast, Kristine listened to it. and she wrote down in all caps, slow it down and explain to your mother. So first, Hi, Mom.

------ Where to find the biomarkers ------ 5:36

Elsa Narration 5:37
So the different biomarkers that Annie mentioned are likely going to be on a report somewhere. If you don't have that information, ask your oncologist. It's probably in the pathology report. A basic version of it.But there might have been other tests as well that have these biomarkers. If your loved one is stage four CRC, then they're probably MSS microsatellite stable. MSS means that they are still working in clinical trials and research to find the best ways to get immunotherapy to work. Sometimes MSS CRC tumors are called cold because it's harder for the immune system to see that they don't belong and to go after them. future episode alert will be on the immunotherapy trial that Kristine is on. one biomarker that wasn't mentioned that you'll see a lot in CRC is APC. Kristine is MSS. She has multiple APC mutations and is KRAS wild. Which means her tumor does not have the KRAS mutation. But none of those words meant anything to us at diagnosis and even for a few months after.

------ MSI - Microsatellite Instability ------ 6:45

Annie 6:47
MSI microsatellite instability is 15% in the earlier stages. So 15% altogether, maybe 10% in stage two and three. And then it goes down to 4% in stage four. And partly it's because the cancer cells are actually easier for our immune system to recognize. And that that's why immunotherapy works They actually have their own immune regulation going on, their own immune surveillance. If you are stage one, two or three and you have microsatellite instability at a certain point, it can be a comfort to know, okay, if I do have recurrence, there is an immunotherapy option and immunotherapy can be curative. are very long, durable responses in the stage four setting.

Elsa Narration 7:37
What What kind of information is out there for people who have HER2 mutations?

Annie 7:41
if you have a HER2 mutation, there's a International Mountaineer trial Phase three that offers first line HER2 targeted treatment that it's already offered in the second line. And you just get people to understand that it's not going to say HER2 on the report, it's going to say IRB two e, r b or erbb2, and that's because of the way that science does their nomenclature.

------ BRAF mutation ------ 8:10

Elsa Narration 8:11
What about people who have BRAF mutations?

Annie 8:15
if you have BRAF microsatellite stability, there is a breakwater trial in the first line I mean, honestly, if you have a BRAF mutation, it's it could be very aggressive. So finding an expert with BRAF, if you're stage three, seeing is a really good idea because you want to have people who are absolutely aware of all your options and can put you in to the best one that they can

------ First line clinical trials based on biomarkers ------ 8:42

Annie 8:41
recommend for you.

Elsa Narration 8:42
It's already hard enough at diagnosis, especially with stage four. Usually the first step is going to be chemo, but with certain biomarkers there are now first line clinical trials. What that means is that if you know your loved one's biomarkers already, they are testing out if an experimental drug or an experimental drug with chemo might be a possible better option than chemo to start.

Annie 9:09
there are trials that are opening up in the first line. right now, a first line, KRAS NRAS trial called Onvansertib. the FDA actually is reviewing this drug. And they made the recommendation, it seems to work better in people who haven't tried Bevacizumab yet. And so we are recommending you move it to the first line so you can find more people who are eligible for the trial. there was research at ASCO just June 2023 that for early onset patients who have high TMB, they might actually have a POLE mutation and people with POLE mutations can actually get immunotherapy in the stage four setting, maybe even in the stage three setting that they're at an NCI. And so it's this interesting kind of combination of

information, what's actionable,what's not actionable, what's even understandable. There's always a value of going to an

------ KRAS and Stage 4 ------ 10:09

Annie 10:09
expert

Elsa Narration 10:10
What should someone with the KRAS mutation be aware of?

Annie 10:14
So I think you have to understand that your biology is going to be different than someone else's.There's might be averages. you might want to find a KRAS expert. there's a KRAS revolution going on. There's dozens and dozens of trials Definitely in KRAS G12C, about 2%, but also about 33% of KRAS patients have G12D. It's even higher in other cancers. And then there's G12V, and then there's G 12 R there's G13D, there's many of these different mutations I mean, we need to get more information about this, but we need to

------ Targeted treatments ------ 10:57

Annie 10:57
like not let ourselves get so scared that we aren't proactive. right now there's so many targeted treatments for BRAF, HER2 and for KRAS and NRAS that knowing your mutation is a really good idea. The KRAS G12C is now in the NCCN guidelines for CRC and Colorectal Cancer. In 2020 a friend of mine was the third person on the Moradi trial in colorectal cancer. So it's now four, five years later and it's now part of the guideline. But she was able to get benefit for herself by doing the trial. to, like, start learning about it early in your disease or have somebody in your life learn early in the disease process so that you have a certain level of comfort versus having to learn it all at once. And the other caveat is that, surgery is more important than mutational targeted treatment in general. So that's the thing is like you want to figure out how do you get to surgery because that's the potentially curative option in CRC. So how do you shrink the tumor? How do you get to the point where the surgeon considers you eligible?

------ It can take time to understand biomarkers ------ 12:18

Elsa 12:18
I remember the date because when I look in my Google photos to remind myself of her list of biomarkers,I look for February 1st, 2022. So like six months after her, initial diagnosis was the first time. that I had her biomarkers this kind of is like showing my learning curve to I was developing the ability to look into them more. So some people that are care partners or patients that like start going into this, you know, searching for information and working with information like right at the very beginning of the diagnosis, I'm kind of amazed because it really it took me a bit to wrap my head around.I needed to find out what I didn't know.

Annie 13:06
I, I think also, I, I totally see where you're coming from. five years ago, like, are you do you have a KRAS or NRAS or BRAF mutation? Or are you KRAS, BRAF NRAS Wild which for people listening wild is the way scientists say that there's no mutation. So if you were KRAS NRAS BRAF wild, You had the ability to do an EGFR inhibitor Cetuximab or Panitumimab but if you had the other mutations, you couldn't do it.

I think like what you guys did a focusing on the best treatment, getting to the best doctors is actually like the most important first line thing you had to take care of yourself. And does it help to, you know, to be thinking about KRAS when you're first diagnosed that there's nothing to do? But things have changed, Like there is a first line KRAS G12C trial, which is like 2% of patients. But

------ NGS (Next Generation Sequencing) reports ------ 14:05

Annie 14:06
I think the problem is and is in these NGS, next generation sequencing reports like some of them like they'll talk about what's actionable but over and over again, you see these reports that are sort of difficult to understand.

Elsa 14:19
yeah, yeah. And they're all in different formats. I mean, technically we have, you know, the pathology report, the SIGNATERA mutation list. She has a Tempus report that listed stuff that Signatera didn't list. So it's in different formats. Some of them look for different things. it's a lot.

------ Inherited mutations ------ 14:41

Annie 14:42
And also that, you know, over time it's something that if it turns out that something is inherited, you'll want to know who your family for testing in most common inherited mutations are. Lynch which you know most people get tested for that in stage four And there's millions of people with Lynch syndrome in the U.S. and like if you diagnose one person with Lynch syndrome, their entire family can then actually help themselves be less at risk. And do you know, more screening, more preventative actions?

Elsa 15:13
definitely

------ Biomarker testing as a standard ------ 15:13

Elsa 15:14
So I know for stage 4, it should be done. Is it standard of care for it to be done at any stage?Do you know?

Annie 15:22
it was part of the NCCN guidelines to be tested at stage four. It's recommended at all stages. Is now part of the guidelines set stage three rectal cancer patients get tested to see if they have microsatellite instability because if they do, the guidelines now has another immunotherapy option that they can, try out. there are people who are getting to NED no evidence of disease on immunotherapy for stage three rectal. It's only about 3% of the patients. But for those 3% immunotherapy might be a way to avoid surgery.

Elsa Narration 16:03
Hopefully that was a helpful intro to Biomarkers and Colorectal Cancer. It might take some time to understand your loved one's cancer more. And that is completely normal. Getting as much information as you can about it is really helpful. That might mean multiple tumor reports. I would highly suggest, even if the cancer doesn't look like it's inherited. Getting a genetic test done as well There's constantly new information and research that's out there. So getting up to date reports might have new biomarkers, mutations, deletions, things that wouldn't have been on a test run by the same company, even just a couple of years ago. if you're interested in learning more about your loved one's cancer, I'm going to have a future episode about how to do some basic research at home and also about clinical trials.

If nothing else comes out of this podcast, then I hope it's that more people get colonoscopies, that people understand how to communicate with people who have cancer. And to talk about your family's medical history. you know, just get your family talking about it.

Outro 17:24
Thank you for joining me for this episode of Care Partners Compass: Navigating CRC. Please listen up for the next episode, which will come out next week. If you subscribe to the podcast on your favorite podcast app, you will know exactly when the next episode comes out.I hope that you'll share the podcast with your friends and family. The transcript of Care Partners Compass: Navigating CRC and additional links can be found on our website

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