Immunotherapy for Colorectal Cancer

Podcast Transcript

Scott Steele: Butts & Guts, a Cleveland Clinic podcast, exploring your digestive and surgical health from end to end.

Hi again, everyone, and welcome to another episode of Butts & Guts. I'm your host, Scott Steele, colorectal surgeon and president of Main Campus here at Cleveland Clinic in beautiful Cleveland, Ohio.

And today, I am having another special guest, one of our own fellow colorectal surgeons, Dr. AJ Keshinro, who is one of our colorectal surgeons here at the Cleveland Clinic.

AJ, welcome to Butts & Guts.

Dr. AJ Keshinro: Hi, Dr. Steele. Thanks for having me. Very excited to be here.

Scott Steele: So good to have you on.

And today, we're going to talk a little bit about immunotherapy for colorectal cancer.

Now, obviously, I know this, but I want our listeners out there to know a little bit about yourself and where you're from, where did you train, and how did it come to the point that you're here at the Cleveland Clinic?

Dr. AJ Keshinro: I always find that question to be a bit tough to answer.

So I was born in America, but grew up in other countries, so Nigeria and England.

I finished high school and undergrad in England before moving back to the States.

I spent most of my time in New York. I did medical school in New York City as well as residency, and then I went on to University of Minnesota where I did my colorectal fellowship and that's what led me to come to Cleveland Clinic because I heard about the job from my mentors at University of Minnesota.

I interviewed, I loved being in Cleveland and I loved my partners, well, future partners at the time, and I ended up coming to Cleveland.

So I've been here for a year and a half and I love it.

Scott Steele: Well, that is fantastic. We're lucky to have you here and whoever hired you was a smart person.

Today, we're going to be talking a little bit more about immunotherapy as treatment for colorectal cancer.

So can you tell our listeners a little of an overview first of colorectal cancer? I know we've had other podcasts on it, but for those who haven't heard it.

And then discuss how common it is in the United States.

Dr. AJ Keshinro: When we talk about colon cancer, it's actually two separate portions. We're talking about cancer in the colon or it could be cancer in the rectum.

So the colon is the large intestine and it's responsible for absorbing water and electrolytes, and the rectum is essentially your internal storage for stool until you're ready to defecate.

So you can get cancer anywhere along those, in the colon or the rectum, and it usually starts off as polyps.

And with time, the polyp, they figure out how to become cancer by mutating, and once they mutate, they can spread and get larger.

So basically, colon cancer or colorectal cancer is very common. Out of the various cancers, it's the third most common cancer in both men and women in the United States, and it's also the second most common cause of cancer-related death in America.

So as you can imagine, in our field, we see this quite a lot and we get to help a lot of people.

Scott Steele: Absolutely. So as I said before, we're going to talk a little bit about immunotherapy for colorectal cancer. So can you give us a high-level overview about what is immunotherapy and how does it work to fight cancer?

Dr. AJ Keshinro: Before I talk about that, I would like to take a step back to talk about what the immune system does at baseline to prevent cancer formation in our body.

So the immune system actually does a very important job of distinguishing between self and non-self, meaning your normal cells and cells that are becoming abnormal.

So the way the body does that is it has checkpoints in place, so protein that is expressed by your cells that your immune cells use to turn off and on a response.

So what could happen is the cancer cells can mimic a normal cell by having those checkpoints and that can allow them to suppress or hide from the immune system.

So it basically targets those checkpoints, the cancer cells has hijacked and basically gets inhibited and allows the body to respond against the cancer again.

So basically, the immunotherapy works by reactivating your own immune system against the cancer cells.

Scott Steele: So anybody needs to turn on the television at any stage and see all sorts of advertisements, immunotherapies kind of everywhere. So can you talk about, are there only certain types of cancer that respond to immunotherapy?

Dr. AJ Keshinro: That is correct. I'll focus more on for colon and rectal cancer, because for different cancers, they have different targets that they look for to see if a patient can get immunotherapy.

So for colon and rectal cancer, one of the more common things that we check for is something called a mismatch repair protein. We tend to call it MMR protein.

And what happens is if a patient has absence of one or more of that protein, they could be a candidate for immunotherapy because it means that the tumor has a high mutational burden, meaning that there's a lot of targets that the immune cells can use to reactivate the immune system against the tumor.

Unfortunately, only a subset of patients do have this MMR deficient cancer. For colon and rectal cancer, that's usually about anywhere between 15 to 20% of diagnosis patients have this MMR deficiency.

Scott Steele: So how is immunotherapy fundamentally different from other types of colorectal cancer treatments?

Dr. AJ Keshinro: So when we talk about the other type of treatments, we usually are talking about chemotherapy, radiation, or surgery.

To kind of focus on chemotherapy, because I think it's the most similar to immunotherapy, it works by patients get essentially cytotoxic medications that will target cancer cells. So it's nonspecific, whereas immunotherapy, like I previously mentioned, it reactivates your own immune system. So it's a little more specific' it's a little more targeted.

So we think of immunotherapy as a targeted therapy, whereas chemotherapy is not. So as a result, chemotherapy tends to have more side effects, because it affects your own normal cells or higher rate than immunotherapy does.

And then when we talk about things like radiation, that's a little more localized, that's not a systemic treatment, meaning it doesn't affect the whole body. It just is very localized, so same part of the body.

So that's completely different to immunotherapy, which, again, I think the most similar is immunotherapy and chemotherapy because they work systemically.

Scott Steele: Why would immunotherapy be recommended instead of other treatments, like surgery, radiation? I know radiation is more key for the rectal cancer. Or is immunotherapy usually recommended in combination with these other cancer treatments? And specifically, obviously, we're talking about colorectal.

Dr. AJ Keshinro: Right. It varies. So to answer this question, I'll break it down into colon and rectal cancer.

So for rectal cancer, the current standard is a combination of chemotherapy, radiation, and surgery. In some patients, they can have something called a clinical response where the cancer completely melts away just by giving the chemo and the radiation and patients do not need surgery.

So one of the things that changed the way we approach this is a groundbreaking trial that was done at Memorial Sloan Kettering in New York City in which they found that giving the immunotherapy alone can actually achieve such a response. So obviously, the patient has to have a MMR deficient cancer, but by giving this, patients can have the cancer completely respond and they can avoid surgery and radiation.

Even if the patient doesn't have a complete response, they can still have a reduction in the tumor size, which could still be very effective and they can subsequently get radiation and surgery.

So, to answer the question for rectal cancer, immunotherapy can be given alone, but even if the patient doesn't have a complete response, they might need a combination of tumor radiation and surgery afterwards as well.

Whereas for colon cancer, right now, it's only approved for metastatic disease or recurrent disease in patients, again, with the MMR deficiency.

So there are ongoing trials trying to look at giving immunotherapy as a first line because, again, if we can recreate a similar situation of what we have with a rectal cancer where the patient have a complete response, then we can avoid surgery altogether or chemotherapy altogether.

But at this current time, for colon cancer, immunotherapy is only given in setting of a current disease or metastatic disease.

So, to answer the question for colon cancer, it could be a combination or it could be given alone if it's metastatic disease.

Scott Steele: So how do doctors determine which colorectal cancer patients might benefit the most from immunotherapies? And not everybody gets it, so how do they sort that out?

Dr. AJ Keshinro: Again, one of the most important things we check for is this MMR protein.

So when a patient has, when they're diagnosed with colon or rectal cancer, the biopsy result is checked reflexively for that MMR deficiency.

So if a patient has that, then immunotherapy is on the table as a potential treatment.

In addition, patient's medical oncologists might run other genetic tests to determine the makeup of the cancer, because there are other markers that might potentially be present.

It will be at a lower rate. They're not as common as the MMR protein, MMR deficiency, but there might be other markers that they might be able to find, which the immunotherapy can help target.

So basically, we do test. We check the biopsy, like I said, and we do genetic tests on the tumor to check for other potential targets.

Scott Steele: So truth or myth, truth or myth. Immunotherapy is typically given in a weekly treatment cycle?

Dr. AJ Keshinro: I would say myth because I think it depends on the actual drug. For most of them, they are given every few weeks. So it could vary from anywhere to two, three, four weeks cycle. So I don't know of any that's given on a weekly basis, but I think the medical oncologist will be more knowledgeable about that.

Scott Steele: So Truth or myth, truth or myth. Even after immunotherapy treatment ends, a body's immune system is able to recognize and attack cancer cells in the future?

Dr. AJ Keshinro: Truth. So by using our own immune system against the cancer, this is a very, very important strategy with immunotherapy.

So with our immune system, we normally have ability to create a long-term memory. So it's the same way when you get a repeat infection, your body responds to it faster. So like, when we talk about viruses and bacterial infection, mostly viruses, but your body responds to it faster, because they had already created those cells that recognize that same offending agent again.

So when it comes to cancer, it's a similar principle. The body creates memory cells that can respond to the cancer cells quickly, and it can provide a very long and sustained response against the cancer cell.

The problem that arises with immunotherapies that the cancer can, again, figure out how to escape this by mutating, so that target is no longer a good way to control the cancer.

Scott Steele: And so what's on the horizon as far as maybe new research or clinical trials to use immunotherapy to treat colorectal cancer?

Dr. AJ Keshinro: So, in addition to ongoing trials, looking at the effect of immunotherapy for rectal cancer, as we talked about, this is very exciting results that we've been having. There's ongoing trials to keep reproducing that finding.

We also are looking at effect of immunotherapy... Well, people are, not me, people looking at the effect of immunotherapy on MMR-proficient tumor. So we've been talking about MMR-deficient tumor up to this point, but majority of the tumor are MMR-proficient.

So right now, we are hoping that we can find with research a way to trigger such a response in those MMR-proficient tumor as well, because they tend to have low immune cells intrinsically. So people are working on ways where we can activate a similar mechanism in those MMR-proficient tumors so that way, we can have immunotherapy as an option for those kinds of cancer.

So that's one of the ongoing works where people are trying to figure out ways to harvest that immune system against it.

And then, in addition to that, there are current clinical trials looking at using immunotherapy as a first line for colon cancer. So typically, currently, when a patient is diagnosed with a non-metastatic colon cancer, we usually go to surgery, and then based on the pathology, they might need chemotherapy.

So the study's ongoing looking at giving that immunotherapy upfront, and hopefully we can avoid surgery. And again, that will be the best, because then you have less complications and patient have a better prognosis.

Scott Steele: Yeah, absolutely. And so now it's time for a quick hitter. It's a chance to get to know you just a little bit better. So first of all, what was your first car?

Dr. AJ Keshinro: My first car was a Hyundai Tucson.

Scott Steele: Fantastic.

Dr. AJ Keshinro: I think, even more interesting, I didn't get my first car until 2022 because I was in New York City, so I never had to drive.

Scott Steele: OMG, I'll leave that one alone. So what is your favorite meal?

Dr. AJ Keshinro: So as I mentioned at the beginning, I'm Nigerian, so I tend to cook mostly Nigerian food. So one of my favorite meal is something called jollof rice. It's kind of a different take on rice where we put pepper and tomato and make it spicy and very flavorful. So if you've never had that, I would recommend it. It's awesome.

Scott Steele: Sounds outstanding. And so what is a favorite trip or one that you want to go on?

Dr. AJ Keshinro: That's a tough question because I'm a huge traveler. I love going to different countries.

More recently, my favorite trip was I went to Machu Picchu. I did the Inca Trail, which was a four-day hike. So camping for three days. I've never done camping before, so that was an interesting experience. I probably should have started with a smaller trip.

And then being in a high altitude and just kind of one with nature and focused on survival. So that was a different experience, and I'm really glad I did it and I really enjoyed it.

Scott Steele: Fantastic. And breathtaking views once you get there. And so finally, do you have a hidden talent or maybe one that most people don't know about?

Dr. AJ Keshinro: Oof. That's a tough one. I don't know if I would say it's a talent, but I'm a great cook. So I think that's probably what I would say. People are always surprised. I hate cooking, so I think that's why people are always surprised. I'm a great cook, but I just don't like cooking.

Scott Steele: That's fantastic. And so give us a final take home message regarding immunotherapy for colorectal cancer.

Dr. AJ Keshinro: I think, overall, being aware as a patient that there is this treatment option is very important, and understanding that it works by reactivating your own immune system against the cancer cells, but also understand that not everybody is a candidate for this.

Automatically, we are checking to see if patients are candidate after the biopsy result comes back. So it is something that is done. And even if you're not a candidate based on the MMR protein, your medical oncologist might do a subsequent test to see if it's something that you might be a candidate for.

This does become more important when it's a recurrent cancer or metastatic cancer. But be aware that this is an exciting treatment that still has ongoing research, and we hope that in the future that we can expand the utility of the immunotherapy to majority of the patient as opposed to a subset of patients.

Scott Steele: Absolutely. And we sure hope the same thing. And so to learn more about colorectal cancer treatment options, please visit clevelandclinic.org/coloncancercare. That's clevelandclinic.org/coloncancercare. And to make an appointment with a colon cancer specialist, please call our Cancer Answer Line at 866.223.8100. That's 866.223.8100. AJ, thanks so much for joining us on Butts & Guts.

Dr. AJ Keshinro: All right, thanks for having me.

Scott Steele: That wraps things up here at Cleveland Clinic. Until next time, thanks for listening to Butts & Guts.