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

A modest pharmacological study undertaken in the United States revealed that every patient treated in the experiment had their disease effectively go into remission, which looks to be a highly hopeful advance for the treatment of rectal cancer.

The medicine used is called dostarlimab and is offered under the brand name Jemperli. It is an immunotherapy drug used to treat endometrial cancer, but this was the first clinical trial to see if it might also be used to treat rectal cancer tumors.

The study team claims that the successful cancer remission witnessed in every trial patient may be unprecedented for a cancer medication intervention, based on the early data revealed thus far.

"I believe this is the first time this has happened in the history of cancer," the senior author of a recent publication describing the results, medical oncologist Luis Diaz Jr. of Memorial Sloan Kettering Cancer Center (MSK), told The New York Times.

It's worth mentioning that the good outcomes have only been reported in 12 individuals so far (the experiment is still ongoing), all of whom had cancers with genetic alterations known as mismatch repair deficiency (MMRd), which is found in about 5%–10% of rectal cancer patients.

Patients with these tumors are less sensitive to chemotherapy and radiation therapies, necessitating surgical excision of the tumors.

MMRd mutations, on the other hand, can render cancer cells more sensitive to immune response, especially when combined with an immunotherapy medication — in this case, a checkpoint inhibitor – that relaxes immune cell constraints, allowing them to more efficiently destroy cancer cells.

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

Patients with these types of rectal tumors typically undergo chemotherapy and radiation therapy before having the tumour surgically removed. Unfortunately, for many patients, this wide range of therapy has long-term repercussions that can last a lifetime.

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

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

The individuals who joined in this study have so far escaped both of these surgeries and their attendant adverse effects due to an incredible stroke of luck.

Patients were given dostarlimab every three weeks for six months in the phase 2 trial, with conventional chemoradiotherapy and surgery to follow if tumors reappeared. That was not the case.

All 12 patients in the experiment had a "clinical complete response" after six months of follow-up, with no indication of tumors visible on MRI scans, PET scans, endoscopy, or biopsy, among other procedures.

"Dr. Cercek told me a team of doctors examined my tests," Sascha Roth, the trial's first patient, recounts. "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 noting that the research – which is being supported by a variety of companies, including GlaxoSmithKline, which makes Jemperli – is still ongoing, and these are simply early findings.

At this time, 12 patients have finished the therapy and have been followed for at least six months.

So far, almost three-quarters of patients have suffered mild or severe side effects, such as rash, itching, tiredness, and nausea – but no cancer has returned, with the median follow-up being one year and some patients, such as Roth, remaining cancer-free for two years.

The experiment is intended to include around 30 individuals in the end. We'll get a better sense of how safe and successful dostarlimab is in people with rectal cancer once we have data from the entire cohort, however much more research in larger groups of patients is still needed.

Until then, oncologist Hanna K. Sanoff of the University of North Carolina at Chapel Hill, who has written a commentary on the findings, advises treating the current findings with both excitement and caution.

According to Sanoff, a clinical complete response to the treatment is not a reliable predictor of long-term cancer control because, despite the fact that checkpoint inhibitors like dostarlimab can have long-lasting effects, cancer regrowth is still expected to occur in a minority of patients with non-operative tumor management, 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 says, adding that larger-scale replication of the results is also needed to be sure of the drug's benefits, which have so far only been seen in a small percentage 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."

With these constraints in mind, there's a lot to be optimistic about; the researchers are already looking into whether their one-of-a-kind immunotherapy method may assist patients with MMRd-positive cancers including stomach, prostate, and pancreatic cancer.

It's still early, and there's a lot we don't know, but Sanoff believes that if more study can repeat the bright potential shown here, we might be watching the emergence of a new type of cancer therapy.

"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," says Sanoff.

"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." 
Every Single Patient in This Small Experimental Drug Trial Saw Their Cancer Disappear Every Single Patient in This Small Experimental Drug Trial Saw Their Cancer Disappear Reviewed by Lilit on June 08, 2022 Rating: 5
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