How a checkpoint inhibitor helped arrest rectal cancer

Host Amber Smith: Upstate Medical University in Syracuse, New York invites you to be "The Informed Patient" with the podcast that features experts from Central New York's only academic medical center. I'm your host, Amber Smith. You may have heard about a clinical trial of patients with rectal cancer, all of whom saw their cancer vanish after taking a particular drug. The amazing results are encouraging even though this study was so small. And here to tell us more about this drug and the trial is Dr. Merima Ramovic. She's a medical oncologist who treats cancers, including rectal cancer. Welcome to "The Informed Patient," Dr. Ramovic.

Merima Ramovic, DO: Hello. Thank you for having me.

Host Amber Smith: So, please tell us about this drug that seems to have worked so well. What's the name of it?

Merima Ramovic, DO: The drug is called Dostarlimab. It is an immunotherapy. Immunotherapy is a treatment that uses the person's own immune system to fight cancer.

Host Amber Smith: I've heard it described as a checkpoint inhibitor. What is that?

Merima Ramovic, DO: Immunotherapy drugs fall under checkpoint inhibitors, and basically part of how our immune system works is by using checkpoint proteins on immune cells. These checkpoints act like switches that need to be turned on, or off, to start an immune response. So cancer cells sometimes find ways to use these checkpoint to avoid being attacked by the immune system. So the immune system doesn't see them, and they continue growing and spreading. So these medications, they're called immune checkpoint inhibitors. So they're preventing cancer cells from turning off the immune system.

Host Amber Smith: So this isn't the first checkpoint inhibitor? This type of medication existed before this drug was created, is that right?

Merima Ramovic, DO: That is correct. Some of the more common drugs that are used, is pembrolizumab, and nivolumab. They're also known as, their brand names are Keytruda, and Opdivo.

Host Amber Smith: And probably people have seen ads for those medications on television.

Merima Ramovic, DO: That is correct. If you have cable TV, I'm sure you have seen an ad for Keytruda and Opdivo.

Host Amber Smith: What are the side effects that are expected with checkpoint inhibitors?

Merima Ramovic, DO: So most patients tolerate the medications really well. Some of the more common side effects that we see could be tiredness, maybe an upset stomach, maybe a rash. Some people can have more severe side effects, like severe diarrhea. It can affect your lungs. But generally it's, it's it's well tolerated.

Host Amber Smith: Can all patients take checkpoint inhibitors, or are there any contraindications?

Merima Ramovic, DO: Not all patients can be treated with checkpoint inhibitors. Patients who have autoimmune disease or who have suspected autoimmune disease, such as multiple sclerosis, rheumatoid arthritis, lupus-- we typically do not treat those patients since it can make their disease a lot worse. And of course, patients who have had a severe or life threatening side effect to the checkpoint inhibitor.

Host Amber Smith: Now this study that took place at Memorial Sloan Kettering Cancer Center, the researchers presented the results at the annual meeting of the American Society of Clinical Oncology in early June, and it was widely covered by the national media. Have you had patients ask you about this new medication?

Merima Ramovic, DO: Yes. I get at least a patient a day who asks about this medication.

Host Amber Smith: How do you explain the research and its significance?

Merima Ramovic, DO: So, the clinical trial looked at patients who have locally advanced rectal cancer, and those patients had what's called mismatch repair deficient cancers. So what is mismatch repair deficiency in a tumor? Well, our DNA, which holds our entire genetic imprint, has a system in place that is called DNA mismatch repair, which corrects any type of mistakes that have happened during DNA replication, when our DNA divides. And, defects in this mismatch repair can lead to what's called microsatellite instability, MSI. So there are patients that have lot of defects, and they're called MSI high. And then there are patients tumors that are MSI stable, so that they don't have it. So when it comes to rectal cancer or colorectal cancer, not a lot of patients have mismatch repair deficiency.

So in this study, they had 12 patients who had locally advanced rectal cancer who had the mismatch repair deficient tumors. And what they did is, they gave them Dostarlimab once every three weeks for a total of six months. And the plan was to follow them, to follow the treatment by standard chemo, radiotherapy and surgery. And patients who had complete clinical response, after completing six months of Dostarlimab therapy would then proceed without chemotherapy and surgery. So, to backtrack a little bit, the typical treatment for locally advanced rectal cancer is chemotherapy with radiation, followed by surgery. So in this study, what they wanted to know is can we give patients immunotherapy and maybe avoid chemotherapy and radiation and surgery? So that's what they set out to find out. So what they saw was quite remarkable, that all of the 12 patients -- so 100% of patients -- had a complete clinical response, meaning when they went back in, they did not see any residual disease. So those patients ended up having a PET (positron emission tomography) scan, endoscopic evaluation, a digital rectal exam or biopsy -- and none of the patients required chemotherapy, radiation therapy or surgery.

Host Amber Smith: This is Upstate's "The Informed Patient" podcast. I'm your host, Amber Smith. I'm talking with Dr. Merima Ramovic. She's a medical oncologist who treats cancer, including rectal cancer. We're talking about the results of a study from earlier this year showing some remarkable, well, beyond improvement -- would you use the word cure, Dr. Ramovic?

Merima Ramovic, DO: We typically don't use the word cure until patients have been without active cancer for five years. We typically say "in remission" or "no evidence of disease."

Host Amber Smith: Hearing about these patients, though, who saw their cancer vanish while they were in this trial, as a medical oncologist, were you surprised to see 100 percent?

Merima Ramovic, DO: I was surprised, but quite happy about these results. This means that for some patients, we may be able to avoid chemotherapy, radiation or surgery.

Host Amber Smith: So the drug Dostarlimab, at this point, has it been FDA approved so that a physician like yourself would be able to prescribe it, if you thought it would help your patient?

Merima Ramovic, DO: We are able to use this drug, yes.

Host Amber Smith: Let me ask you, how common is complete remission in someone being treated for rectal cancer. Do you see that often?

Merima Ramovic, DO: So our goal when we set out to treat patients with rectal cancer is obviously cure. Most patients, or many patients, are cured. However, at this time when I sit down with a patient and I tell them the plan, there are no predictors that I can use or markers that will tell me patient A is going to be cured, and patient B will not be cured.

Host Amber Smith: So there's no way to predict how the treatment is going to work?

Merima Ramovic, DO: There is no way to predict.

Host Amber Smith: At this point, does treatment usually include radiation, and surgery, and chemotherapy of some sort, or medication of some sort?

Merima Ramovic, DO: Standard treatment for rectal cancer is chemotherapy along with radiation. So the chemotherapy allows the radiation to work better. So it it's a radiation sensitizer. And the radiation prevents or is supposed to prevent a local recurrence. This is usually followed by surgery, and then by additional chemotherapy. Sometimes we give chemotherapy with radiation, followed by chemotherapy, followed by surgery.

Host Amber Smith: So if larger trials are done with more patients of this Dostarlimab, and treatment standards change, would that potentially mean that patients could avoid radiation and surgery in order to have rectal cancer treated?

Merima Ramovic, DO: That is correct. We need to continue following, and they are following, these 12 patients to see how well they're doing. When the study was published, some patients were followed as long as 25 months, so couple years out. But we still need more work. More work has to be done.

Host Amber Smith: Would the drug potentially be used for other cancers beyond rectal cancer? Or is it designed just for rectal cancer?

Merima Ramovic, DO: This drug, potentially, can be used for other cancers.

Host Amber Smith: Do people who are newly diagnosed with rectal cancer, or any type of GI cancer, do they typically undergo genetic testing of their tumors?

Merima Ramovic, DO: There is different types of genetic testing. So there's genetic testing in patients who have a strong family history of cancer, where we suspect hereditary syndromes. So that's one type of genetic test that we do. The best example is the BRCA mutation for breast cancer patients. So there's that genetic testing.

And then there is molecular testing, where we look at the genetics of the cancer itself, of the cancer cells themselves. We do do testing on all stage 4 cancer patients, and almost all stage 3 cancer patients. There's some exceptions here or there.

Host Amber Smith: So you would need the results from that testing before you could say whether Dostarlimab might help somebody, is that right?

Merima Ramovic, DO: That's correct.

Host Amber Smith: Well, I know that you're excited about the results of this drug trial. What do you say to the patients who come in and ask about whether it could be an option for them or their loved ones?

Merima Ramovic, DO: So, when I first meet with patients and their family or friends in the exam room -- although due to COVID the amount of persons allowed and the exam room is limited, and I hope that's going to change soon, as I want important people in the exam room to hear what we have to say -- so when a person comes into the office, I typically review the findings, the imaging, and I come up with a treatment plan. If the mismatch repair testing hasn't been done, I will order that. And the turnaround is pretty quick. So the treatment decision is made in the beginning, before we start treatment.

Host Amber Smith: Well, that's good to know. Thank you so much for making time for this interview, Dr. Ramovic.

Merima Ramovic, DO: Thank you.

Host Amber Smith: My guest has been Upstate medical oncologist, Dr. Merima Ramovic. "The Informed Patient" is a podcast covering health, science and medicine brought to you by Upstate Medical University in Syracuse, New York, and produced by Jim Howe. Find our archive of previous episodes at upstate.edu/informed This is your host Amber Smith, thanking you for listening.