In what appears to be a very promising breakthrough for the treatment of rectal cancer, a small drug trial conducted in the U.S. found that all patients treated in the experiment had their cancer successfully in remission.
The drug administered, called dostarlimab and sold under the brand name Jemperli, is an immunotherapy drug used in the treatment of endometrial cancer, but this was the first clinical study of whether it was also effective against rectal cancer tumors.
The first results reported so far suggest that it is surprisingly effective, with the research team saying that successful cancer remission observed in all patients in the trial may be unprecedented for a cancer drug intervention.
“I think this is the first time this has happened in the history of cancer,” medical oncologist Luis Diaz Jr. told The New York Times. of the Memorial Sloan Kettering Cancer Center (MSK), lead author of a new article reporting the results. .
It is worth noting that the positive results have only been seen in 12 patients so far (the trial is ongoing), all of whom had tumors with genetic mutations called mismatch repair deficiency (MMRd), observed in a subset of ‘approximately 5-10 percent of patients. patients with rectal cancer.
Patients with these tumors tend to be less sensitive to chemotherapy and radiation treatments, which increases the need to surgically remove their tumors.
However, MMRd mutations can also make cancer cells more vulnerable to the immune response, especially when it is enhanced by an immunotherapy agent, in this case, a control point inhibitor, which triggers restrictions on immune cells so they can kill cancer cells more effectively.
“When these mutations accumulate in the tumor, they stimulate the immune system, which attacks the cancer-laden cancer cells,” says Diaz. “We thought, ‘Let’s try it before cancer metastasizes as the first line of treatment.’
Normally, patients with this type of rectal tumor may expect to undergo chemotherapy and radiation therapy before surgical removal of the cancer. Unfortunately, for many patients this range of treatments has lasting consequences that can last for the rest of their lives.
“Standard treatment for rectal cancer with surgery, radiation, and chemotherapy can be especially difficult for people because of the location of the tumor,” says MSK Medical Oncologist Andrea Cercek, the study’s lead author.
“They can suffer from intestinal and bladder dysfunction that alters life, incontinence, infertility, sexual dysfunction and more.”
With a surprising turn of luck, patients who enrolled in this trial have so far completely avoided these procedures and their associated side effects.
In the phase 2 study, patients received dostarlimab every three weeks for six months, with standard chemoradiotherapy and surgery to follow if the tumors returned. They didn’t.
After six months of follow-up, the 12 patients in the trial showed a “complete clinical response,” with no evidence of MRI tumors, PET scans, endoscopy, and biopsy, among other tests.
“Dr. Cercek told me that a team of doctors examined my tests,” says Sascha Roth, the first patient enrolled in the trial. “And because they didn’t find any signs of cancer, Dr. Cercek said there was no reason for me to endure radiation therapy.”
It is worth noting that the research, funded by many organizations, including the pharmaceutical company GlaxoSmithKline, which manufactures Jemperli, has not yet been completed, and these are only preliminary results that have been reported so far.
Currently, a total of 12 patients have completed treatment and at least six months of follow-up.
About three-quarters of patients have so far experienced mild to moderate side effects, such as rash, itching, fatigue, and nausea, but so far none have seen an increase in cancer, with an average follow-up of one year and some patients, such as Roth, without cancer for two years.
Ultimately, the trial is expected to include about 30 patients. When we have data on the whole group, we will have a more complete picture of how safe and effective dostarlimab is in patients with rectal cancer, although many more studies are still needed in larger groups of patients.
So far, we need to treat the current results with optimism and caution, says oncologist Hanna K. Sanoff of the University of North Carolina at Chapel Hill, who has written a comment on the findings.
According to Sanoff, a complete clinical response to treatment is not a substitute for long-term cancer control, as although control point inhibitors such as dostarlimab may have effects for years, growth is generally expected. cancer still occurs in a minority of patients with tumors. they are managed non-surgically, much less with an experimental treatment like this.
“Little is known about how long it takes to find out if a complete clinical response to dostarlimab is equivalent to a cure,” says Sanoff, noting that we also need large-scale replication of the results to be sure of the benefits of the drug. so far they have only been seen in a minority of patients with MMRd tumors.
“It is unknown at this time what he will do after leaving the post.
Given these warnings, there are many hopes here; researchers are already investigating whether their unique immunotherapy approach could also help patients with other tumors that have MMRd, such as some types of cancer of the stomach, prostate, and pancreas.
These are the early days, and there are still many things we don’t know, but if more research can replicate the bright promise hinted at here, we could witness the development of a new type of cancer therapy, Sanoff says.
“Despite these uncertainties, Cercek and his colleagues and patients who agreed to give up standard treatment for a promising future but unfamiliar with immunotherapy have provided what may be an early view of a revolutionary change in treatment.” , writes Sanoff.
“If immunotherapy can be a curative treatment for rectal cancer, eligible patients may no longer have to accept a functional commitment to cure themselves.”
The findings are published in The New England Journal of Medicine.