by In an unprecedented clinical study, a dozen rectal cancer patients saw their tumors disappear after receiving an experimental drug called dostarlimab, and none of the patients experienced significant side effects from the treatment.
“I believe this is the first time in the history of Cancer“As this is the first cancer study in which every patient went into remission, Dr. Luis Alberto Diaz, Jr., co-investigator and medical oncologist at Memorial Sloan Kettering (MSK) Cancer Center, said the New York Times (opens in new tab).
It’s too early to say if the patients will all remain in remission or if the drug will work in others with different types of rectal cancer; but the results are “reason for great optimism,” said one expert. Details of the small study, conducted at the MSK Cancer Center in New York City, were published Sunday (June 5) in New England Journal of Medicine (opens in new tab) (NEJM).
The 12 study participants all have a type of rectal cancer that tends to be resistant to chemotherapy and radiation and is known as “mismatch-repair-deficient” rectal cancer. This type of cancer occurs when the cells’ mechanisms for repairing DNA begin to falter. Usually, since cells make copies of theirs DNSspecific enzymes work to correct any typos in the genetic code. However, when the genes that code for these copy-editing enzymes go wrong, cells end up accumulating DNA typos that can lead to cancer, the researchers said National Cancer Institute (opens in new tab).
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According to the NEJM report, an estimated 5 to 10% of rectal cancer patients have a mismatch repair deficiency. The cancers’ resistance to chemotherapy and radiation means affected patients are more likely to need a proctectomy — an operation that removes all or part of the rectum, which can cause permanent nerve damage, as well as intestinal, urinary and sexual dysfunction.
The MSK researchers started their study hoping to help patients avoid these potential side effects of surgery.
They suspected dostarlimab might help shrink or eliminate patients’ tumors based on previous studies of a drug in the same class called pembrolizumab, the Times reported. Both pembrolizumab and dostarlimab are “checkpoint inhibitors,” drugs that enhance immune ability of cells to recognize and attack cancer cells.
Pembrolizumab showed benefits as a first-line treatment in patients with metastatic mismatch-repair-deficient cancer, ie patients whose tumors had started to spread throughout the body. In these patients, the drug helped stabilize, shrink, or eliminate their tumors, thereby prolonging their lives. In the new study, the MSK researchers wanted to see what a similar drug could do in patients with local cancer that hasn’t metastasized yet.
Study participants received 500 milligrams of dostarlimab every three weeks for six months. The initial expectation was that after this treatment, most patients would still have to undergo the standard combination of chemotherapy, radiation therapy, and possibly surgery. Instead, the cancers of all 12 patients healed completely with dostarlimab alone. Her tumors were undetectable on physical examination, endoscopy, PET and MRI scans. About a year later, none of the patients needed further treatment and none of their cancers had grown back, the team wrote in their report.
Even now, more than two years later, “no patient required chemoradiotherapy or surgery, and no cases of progression or recurrence were noted during follow-up,” according to a expression (opens in new tab) by MSK.
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“These results give cause for great optimism,” but without further research, dostarlimab may not yet replace standard, curative treatment for rectal cancer with misfit repair, says Dr. Hanna Sanoff, an oncologist at the Lineberger Comprehensive Cancer Center at the University of North Carolina, wrote in a comment (opens in new tab) of the new study published in NEJM.
In some cases, patients’ responses to checkpoint inhibitors can last for years, but in others the effects wear off much faster, she wrote. And generally, cancer regrowth occurs in about 20% to 30% of patients whose condition is treated without surgery. “Very little is known about the time it takes to find out if a complete clinical response to dostarlimab is equivalent to a cure,” said Sanoff.
Despite these uncertainties, the new study results are “compelling” and suggest there could be a dramatic shift in rectal cancer treatment in the future, she wrote. “If immunotherapy can be a curative treatment for rectal cancer, eligible patients may no longer need to make functional compromises to be cured,” she said.
“While longer follow-up is required to assess duration of response, practice is changing for patients with [mismatch repair-deficient] locally advanced rectal cancer,” Diaz said in the MSK statement.
Originally published on Live Science.
