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Medical illustration of colorectal cancer. (ChrisChrisW/Getty Images)HEALTH

Every Single Patient in This Small Experimental Drug Trial Saw Their Cancer Disappear

PETER DOCKRILL

6 JUNE 2022

In what appears to be a very promising breakthrough for the treatment of rectal cancer, a small drug trial conducted in the US found every patient treated in the experiment had their cancer successfully go into remission.

The medication given, 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 investigation of whether it was also effective against rectal cancer tumors.

The early results reported so far suggest it is surprisingly effective, with the research team saying the successful cancer remission seen in every trial patient may be unprecedented for a cancer drug intervention.

“I believe this is the first time this has happened in the history of cancer,” medical oncologist Luis Diaz Jr. from Memorial Sloan Kettering Cancer Center (MSK), the senior author of a new paper reporting the results, told The New York Times.

It’s 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), seen in a subset of approximately 5–10 percent of rectal cancer patients.

Patients with such tumors tend to be less responsive to chemotherapy and radiation treatments, which increases the need for surgical removal of their tumors.

However, MMRd mutations can also make cancer cells more vulnerable to immune response, especially it’s bolstered by an immunotherapy agent – in this case, a checkpoint inhibitor, which unleashes restrictions on immune cells so they can more effectively kill cancer cells.

“When those mutations accumulate in the tumor, they stimulate the immune system, which attacks the mutation-ridden cancer cells,” Diaz says. “We thought, ‘Let’s try it before cancer metastasizes as a first line of treatment’.”

Ordinarily, patients with these kinds of rectal tumors might expect to undergo chemotherapy and radiation therapy prior to surgical removal of the cancer. Unfortunately, for many patients this gamut of treatments comes with long-lasting consequences that can last the rest of their life.

“The standard treatment for rectal cancer with surgery, radiation, and chemotherapy can be particularly hard on people because of the location of the tumor,” says MSK medical oncologist Andrea Cercek, the first author of the study.

“They can suffer life-altering bowel and bladder dysfunction, incontinence, infertility, sexual dysfunction, and more.”

In an amazing turn of luck, the patients who enrolled in this trial have so far completely avoided both these procedures and their associated side effects.

In the phase 2 study, patients were given dostarlimab every three weeks for six months, with standard chemoradiotherapy and surgery set to follow if tumors returned. They didn’t.

After six months of follow-up, all 12 patients in the trial showed a “clinical complete response”, with no evidence of tumors to be seen via MRI scans, PET scans, endoscopy, and biopsy, among other tests.

“Dr. Cercek told me a team of doctors examined my tests,” explains Sascha Roth, the first patient enrolled in the trial. “And since they couldn’t find any signs of cancer, Dr. Cercek said there was no reason to make me endure radiation therapy.”

It’s worth nothing that the research – funded by numerous organizations, including the pharmaceutical company GlaxoSmithKline, which manufactures Jemperli – isn’t over yet, and these are only preliminary results being reported so far.

At present, a total of 12 patients have completed the treatment and undergone at least six months of follow-up.

About three-quarters of patients so far have experienced mild or moderate side effects, including rash, itching, fatigue, and nausea – but none have so far seen a regrowth in cancer, with the median follow-up being at one year, and some patients, like Roth, being cancer-free for two years.

Ultimately, the trial is expected to include about 30 patients. When we have data on the whole group, we’ll have a fuller picture of how safe and effective dostarlimab is in patients with rectal cancer, although much more study is yet needed in broader groups of patients.

Until such time, we need to treat the current results with both optimism and caution, says oncologist Hanna K. Sanoff from the University of North Carolina at Chapel Hill, who has written a commentary on the findings.

According to Sanoff, a clinical complete response to the treatment is not a surrogate for long-term cancer control, as even though checkpoint inhibitors like dostarlimab can have effects lasting years, cancer regrowth is generally expected to still occur in a minority of patients where tumors are managed non-operatively, let alone with an experimental treatment like this.

“Very little is known about the duration of time needed to find out whether a clinical complete response to dostarlimab equates to cure,” Sanoff explains, noting that we also need larger-scale replication of the results to be sure of the drug’s benefits, which so far have only been seen in a minority of patients with MMRd tumors.

“Whether the results of this small study conducted at Memorial Sloan Kettering Cancer Center will be generalizable to a broader population of patients with rectal cancer is also not known.”

Bearing these caveats in mind, there’s a lot to be hopeful for here; the researchers are already investigating whether their singular immunotherapy approach could also help patients with other tumors that have MMRd, such as some types of stomach, prostate, and pancreatic cancer.

It’s early days, and there’s still a lot we don’t know, but if further research can replicate the bright promise hinted at here, we might be witnessing the development of a new kind of cancer therapy, Sanoff says.

“Despite these uncertainties, Cercek and colleagues and their patients who agreed to forgo standard treatment for a promising but unknown future with immunotherapy have provided what may be an early glimpse of a revolutionary treatment shift,” Sanoff writes.

“If immunotherapy can be a curative treatment for rectal cancer, eligible patients may no longer have to accept functional compromise in order to be cured.”

The findings are reported in The New England Journal of Medicine.null© ScienceAlert US LLC. All rights reserved

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