A small group of people with rectal cancer just experienced something of a miracle as their cancer simply vanished after an experimental treatment.
In a very small clinical trial, 18 patients took a drug called Dostarlimab for around six months, and in the end, every one of them saw their tumours disappear.
Dostarlimab is a drug with laboratory-produced molecules that act as substitute antibodies in the human body. All 18 rectal cancer patients were given the same drug and as a result of the treatment, cancer was completely obliterated in every patient - undetectable by physical exam; endoscopy; positron emission tomography or PET scans or MRI scans, Memorial Sloan Kettering Cancer Center published the article on their website on Wednesday.
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The MSK clinical trial was investigating, if immunotherapy alone could beat rectal cancer.
100% remission of rectal cancer
In every case, the rectal cancer disappeared after immunotherapy — without the need for the standard treatments of radiation, surgery, or chemotherapy — and the cancer has not returned in any of the patients, who have been cancer-free for up to two years.
“It’s incredibly rewarding,” says Dr Cercek, “to get these happy tears and happy emails from the patients.
Her co-investigator, MSK medical oncologist Luis Diaz, Jr, is equally thrilled. He’s spent his career studying how to defeat cancer with immunotherapy.
Using immunotherapy earlier to target a genetic mutation
Drs Cercek and Diaz explain that their team’s research was sparked by two key ideas.
The first premise, says Dr Diaz, is to figure out precisely which patients benefit most from immunotherapy, so they can receive it right away. “Immunotherapy has proven successful in treating a subset of patients with colon and rectal cancer that has metastasized, meaning spread to other tissues.”
Between 5 per cent and 10 per cent of all rectal cancer patients are thought to have MMRd tumors, including all the patients in the MSK clinical trial that Sascha participated in. There are 45,000 Americans diagnosed a year with rectal cancer.
“An MMRd tumor develops a defect in its ability to repair certain types of mutations that occur in cells. When those mutations accumulate in the tumor, they stimulate the immune system, which attacks the mutation-ridden cancer cells,” says Dr. Diaz, who heads the MSK division of Solid Tumor Oncology and holds the Grayer Family Chair.
But cancer has a trick up its sleeve to stop the immune system from doing its job.
Helping the immune system overcome rectal cancer
Immune cells contain a safeguard called a checkpoint, to prevent them from attacking normal cells. Cancer cells can trip this safeguard and shut down immune cells, allowing a tumor to hide and grow.
However, immunotherapy can turn the tables yet again.
An immunotherapy agent called a checkpoint inhibitor releases the brake on an immune cell, freeing it to recognize and attack cancer cells. “When the brakes are taken off the immune cells, MMRd cells look especially strange because they have so many mutations. So the immune cells attack with much more force,” explains Dr Cercek.
Dr Diaz’s pioneering research in treating cancer with immunotherapy had already shown that checkpoint inhibitors could “help people with MMRd colorectal tumors that have spread,” he says. “We thought, ‘Let’s try it before cancer metastasizes as a first line of treatment.’ ”
Avoiding life-altering side effects
The second premise of the clinical trial was to avoid the toxicity often associated with treatment for rectal cancer.
Dr Cercek explains: “Our first duty is to save our patient’s life. But the standard treatment for rectal cancer with surgery, radiation, and chemotherapy can be particularly hard on people because of the location of the tumor.” She continues, “They can suffer life-altering bowel and bladder dysfunction, incontinence, infertility, sexual dysfunction, and more.”
Dr Diaz notes, “Obviously, that can lead to a lot of self-esteem and psychiatric issues as well.”
To avoid these toxicities, many approaches to rectal cancer try to shrink the tumor as much as possible with chemotherapy and radiation to facilitate surgery. Drs Cercek and Diaz surmised that immunotherapy in MMRd patients may similarly shrink the tumor to enable a more successful surgery.
But Dr Cercek proposed going further: In patients where the immunotherapy caused the cancer to completely disappear, doctors would omit chemotherapy, radiation, and surgery — and, instead, closely monitor for any signs of recurrence. Dr Diaz says this decision by Dr Cercek was “a world-class moment” that promised to change the lives of patients — if it worked.
All patients in the trial must have stage 2 or 3 rectal tumors that are MMRd — which makes their cancer particularly sensitive to immunotherapy. The patients were given the checkpoint inhibitor dostarlimab (Jemperli) intravenously every three weeks, for six months.
Their tumors were closely tracked, Dr Diaz explains, “using imaging, visualization such as endoscopy, as well other methods.”
Potential help for other cancers
As MSK’s rectal cancer trial continues, Dr Diaz says he hopes “it’s the tip of the iceberg.” He explains that “we are investigating if this same method may help other cancers where the treatments are often life-altering and tumors can be MMRd. We are currently enrolling patients with gastric (stomach), prostate, and pancreatic cancers.”
Dr Diaz has coined a term for this new method of using immunotherapy alone to target MMRd tumors, calling it “immunoablative” therapy — that means using “immunotherapy to replace surgery, chemotherapy, and radiation to remove cancer.” Dr Diaz says, “That might sound futuristic — but in this trial, we have a clinical example where that happened.”
Today, nearly two years after she began the trial and remains cancer free, Sascha continues to live a normal life. She runs a family-owned home-furnishing and interior design business and often speaks to people facing rectal and other cancers.
“My whole experience has been like a dream,” she says. “MSK research and cancer care is simply years and years ahead of where other hospitals — even really good ones — are or should be.”
