A small trial testing a rectal cancer immunotherapy is delivering astonishing results: every single participant — fourteen, in all — has had their disease go into complete remission.
“I believe this is the first time this has happened in the history of cancer,” Luis Diaz, co-investigator of the trial at Memorial Sloan Kettering Cancer Center (MSK), told the New York Times.
Rectal cancer: Every year, about 45,000 people in the US are diagnosed with cancer of the rectum, in the final several inches of the large intestine.
Patients will often undergo chemotherapy or radiation to shrink their tumors, before trying to remove them through surgery. Alternatively, doctors might remove the tumors first, then suggest chemo or radiation therapy to eliminate any lingering cancer cells.
Rectal cancer treatments themselves can cause lifelong health problems.
When rectal cancer is caught early — before it has time to spread to other areas of the body — these treatments have a high success rate, with 91% of patients living at least five years after diagnosis.
However, the treatments themselves can cause lifelong health problems, including incontinence, infertility, and sexual dysfunction, in many cases leading to self-esteem and psychiatric issues.
Cancer immunotherapy: Surgery, chemotherapy, and radiation aren’t the only cancer treatment options — there’s also immunotherapy, a type of treatment that changes or boosts the body’s own immune system to attack the disease.
Normally, our immune systems help us stay healthy by attacking foreign invaders, such as viruses and bacteria. But proteins called “immune checkpoints” act as an important brake on immune cells, preventing them from going overboard and attacking healthy cells.
Some cancers can take advantage of these checkpoints to hide from the immune system. An immunotherapy called a “checkpoint inhibitor” can release the brake, allowing the immune system to identify and attack cancer cells.
“When the brakes are taken off the immune cells, MMRd cells look especially strange.”
Andrea Cercek
The trial: For the trial at MSK, researchers wanted to test whether immunotherapy alone could help a specific subset of rectal cancer patients: ones with mismatch repair-deficient (MMRd) tumors that had not spread beyond the rectum.
About 5% to 10% of rectal cancer patients have MMRd tumors, which have a lot of genetic mutations in their DNA. In a previous trial, in which patients’ rectal cancer had already spread, a checkpoint inhibitor worked particularly well against this type of tumor.
“When the brakes are taken off the immune cells, MMRd cells look especially strange because they have so many mutations,” said co-investigator Andrea Cercek. “So the immune cells attack with much more force.”
For the new trial, patients received a checkpoint inhibitor that is already used to treat endometrial cancer (dostarlimab) intravenously every three weeks for six months — and the response was overwhelmingly positive.
“The immunotherapy shrank the tumors much faster than I expected,” said Cercek. “My research nurse Jenna Sinopoli would tell me, ‘The patient has only received one treatment and already they’re not bleeding anymore and their terrible pain has gone away.’”
“Before I came to MSK, oncologists at another medical center told me I needed chemo, radiation, and surgery.”
Sascha Roth
That was just the beginning, though — all 14 patients who’ve received the treatment so far have had their rectal cancer go into complete remission, and they’ve all been cancer-free ever since.
“Before I came to MSK, oncologists at another medical center told me I needed chemo, radiation, and surgery,” said Sascha Roth, the trial participant who has been in remission the longest (nearly two years). “To instead get immunotherapy infusions every few weeks in New York with no side effects seemed like a cakewalk in comparison.”
Diaz has come up with a name for this “cakewalk” approach to fighting cancer: immunoablative therapy.
“[It means using] immunotherapy to replace surgery, chemotherapy, and radiation to remove cancer,” he said. “That might sound futuristic — but in this trial, we have a clinical example where that happened.”
“We are investigating if this same method may help other cancers.”
Luis Diaz
Looking ahead: The researchers are looking forward to testing the ability of immunoablative therapy to help other types of cancer patients.
“We are investigating if this same method may help other cancers where the treatments are often life-altering and tumors can be MMRd,” said Diaz. “We are currently enrolling patients with gastric (stomach), prostate, and pancreatic cancers.”
The rectal cancer trial is also ongoing, and the researchers urge anyone battling the disease to get tested to see if their tumors are MMRd and contact MSK if they are.
“No matter what stage the cancer is, we have a trial at MSK that may help you,” said Diaz.
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