A recent clinical trial using an immunotherapeutic “checkpoint inhibitor” completely eradicated colorectal cancer in all 18 participants.
It is virtually unheard of — the stuff of science fiction or daydreams — but a recent clinical trial has eradicated cancer in every trial participant, causing the patients’ cancer to go into complete remission.
The trial was small, just 18 colorectal cancer patients, but that doesn’t make the results less astonishing. All 18 patients were given the immunotherapy drug dostarlimab, and all 18 left the hospital on their last day of treatment cancer-free.
According to Dr. Omkar Marathe, Medical Director of Clinical Trials at the Oncology Institute in Long Beach, California, dostarlimab was first approved by the U.S. Food and Drug Administration as a treatment option for patients with a specific subtype of advanced endometrial cancer — a mismatch repair protein deficiency.
That’s why colorectal cancer was the focus of the recent study. According to Marathe, colorectal cancer is the cancer that has the largest percentage of patients with this gene mutation (the mismatch repair deficiency), making up around 5% to 10% of colorectal cancer patients. “Those patients are the ones that we know benefit from immunotherapy such as dosatarlimab,” Marathe says.
According to the National Cancer Institute, there are currently 19 clinical trials using dostarlimab for a wide variety of cancers — primarily breast and endometrial cancers, but also cancers of the liver, lungs and others. It’s clear doctors and researchers believe this drug holds promise for cancers that might otherwise be unresponsive to standard treatment plans due to this specific gene mutation.
But that’s not the only reason the study focused on colorectal cancer. According to Dr. Mohammed Al Hallak from Detroit’s Karmanos Cancer Institute, colorectal cancer has an outsized impact on a patient’s quality of life. “It is because of the negative impact of the radiation in this area,” he says, noting that radiation affects the bladder and bowels. Some patients receive surgery to remove the tumor entirely, which can result in a permanent colostomy. “[This] impacts the patients quality of life significantly,” Al Hallak says. “Doing this treatment … makes a lot of sense because of the very large impact.”
The 18 patients entered the trial without expecting miracles. The study’s doctors published an editorial in the New England Journal of Medicine in June 2022, citing that routine treatment of colorectal cancer includes chemotherapy, radiation, and surgery — this is the colorectal “standard of care,” which results in a three-year disease-free survival rate of 77%. However, these treatment options can also result in long-term side effects, including infertility and sexual dysfunction, among others. However, no patient treated with dostarlimab has experienced these outcomes as a result of the drug to date.
There are multiple types of immunotherapy to treat cancer. Most work harmoniously with the immune system, which results in less negative side effects than those related to chemotherapy, which kills both healthy and cancerous cells without distinction. Dostarlimab is a type of immunotherapy known as a “ checkpoint inhibitor.” These immunotherapy drugs work by “unmasking” cancer cells to allow the immune system to target and kill these cells, specifically.
“It is because of the negative impact of the radiation in this area. Some patients receive surgery to remove the tumor entirely, which can result in a permanent colostomy. [This] impacts the patients quality of life significantly. Doing this treatment … makes a lot of sense because of the very large impact.”
Trials with other types of checkpoint inhibitors have proved promising, but the dostarlimab trial was special, as treatment began on patients before their cancer had a chance to spread. But this is also why the trial was a little risky, and initially difficult to secure funding, according to Dr. Luis A. Diaz Jr., one of the authors of the study, in a June 2022 article in the New York Times. Researchers proposed to alter colorectal cancer’s standard of care, bypassing chemotherapy and radiation, which meant participants would potentially allow the cancer to grow and spread.
Al Hallak says his initial focus is to shrink a patient’s tumor, so those who receive surgery are less at risk of damaging the digestive tract. “Our job in the clinical practice is to try to shrink that rectal cancer as much as possible so the surgeon, when they go in to remove it, is able to … keep everything connected, and not need to do a colostomy,” Al Hallak says. “With this new trial … those lucky patients did not have to do any chemo, did not have to do any radiation, did not have to get the surgery [and] they are now monitoring them to make sure none of the cancer comes back.”
Trial participants will need to be monitored for the next three to five years to ensure their “cure” holds, according to Al Hallak. It’s also important to note this trial focused on patients with a rare genetic signature in their tumors, and additional trials involving larger numbers of patients will need to be completed to better understand potential side effects and long-term efficacy of dostarlimab. However, these recent positive results are almost certain to ensure further studies into this drug and others like it — for cancers across the spectrum. “The more we treat, the more we see results, we can actually bring it for FDA approval so we can use it as treatment in practice outside of clinical trial,” Al Hallak says.