Immunotherapy Drug Spares Cancer Patients From Grisly Surgeries and Harsh Therapies

When a person develops solid tumors in the stomach or esophagus or rectum, oncologists know how to treat them. But the cures often come with severe effects on quality of life. That can include removal of the stomach or bladder, a permanent colostomy bag, radiation that makes patients infertile and lasting damage from chemotherapy.

So a research group at Memorial Sloan Kettering Cancer Center, using a drug from the pharmaceutical company GSK, tried something different.

The researchers started with a group of 103 people. The trial participants were among the 2 to 3 percent of cancer patients with tumors that should respond to immunotherapy, a drug that overcomes barriers that prevent the immune system from attacking cancers.

But in clinical trials, immunotherapy is not supposed to replace the standard treatments. The researchers, led by Dr. Luis A. Diaz Jr. and Dr. Andrea Cercek, decided to give dostarlimab, an immunotherapy drug, on its own.

The result was stunning, and could bring hope to the limited cohort of patients contending with these cancers.

In 49 of the patients, who had rectal cancer, the tumors disappeared and, after five years, have not recurred. Cancers also vanished for 35 of 54 patients who had other cancers, including in the stomach, esophagus, liver, endometrium, urinary tract and prostate.

Out of all 103 patients, cancers recurred in only five. Three got additional doses of immunotherapy and one, whose tumor recurred in a lymph node, had the lymph node removed. Those four patients so far have no evidence of disease. The fifth patient had additional immunotherapy that made the tumor shrink.

The investigators reported their results Sunday at the annual meeting of the American Association for Cancer Research and in a paper published in The New England Journal of Medicine.

The results, said Dr. Bert Vogelstein, an oncologist at Johns Hopkins in Baltimore, are “groundbreaking.”

Earlier phases of the drug’s development occurred in his lab, and he has watched its progress with amazement.

“Twenty or 30 years ago, the idea that you could take large tumors of many different organs and treat them without doing surgery would seem like science fiction,” he said. But, he added, the discovery did not spring full blown into the minds of researchers. Instead, he noted, it builds on 40 years of research “starting with very basic science.”

The reason immunotherapy even had a chance against these large tumors is because the patients’ tumors had what is known as mismatch repair mutations in their genes that prevented them from fixing DNA damage. As a result, such tumors are studded with unusual proteins that signal the immune system to destroy them. But tumors put up a shield that blocks immune system attacks. Immunotherapy pierces the shield and allows the immune system to destroy the tumors.

For patients like those in the study, said Dr. Michael Overman, a specialist in gastrointestinal cancer at MD Anderson Cancer Center in Houston, the results show immunotherapy without chemotherapy, radiation treatments or surgeries is a valid treatment “and it is so logical we should be doing it.”

But, for now, that may not be so easy. The drug costs about $11,000 per dose, and patients need nine infusions over six months. In order to get insurance coverage, the drug has to be included in clinical guidelines, sets of recommendations for treatments produced by professional organizations.

It is approved as a treatment for uterine cancers with mismatch repair mutations and is included in clinical guidelines for the treatment of rectal cancer, based on an earlier small study. But patients with other cancers might have trouble getting the drug, Dr. Diaz said. Memorial Sloan Kettering, though, is still recruiting for its clinical trial, so patients who have tumors with mismatched repair mutations and qualify for the study can get the drug free.

For some patients, immunotherapy has been miraculous. It can have side effects — the most common among patients in the study were fatigue, rash and itching. Rarer side effects included lung infections and encephalitis.

Maureen Sideris, 71, of Amenia, N.Y., found out she had cancer after she tried to eat a hamburger.

“It would not go down,” she said. There was some sort of blockage. It turned out to be a tumor at the juncture of her stomach and esophagus.

She went to Sloan Kettering in 2022. Her surgeon told her that she needed surgery, chemotherapy and radiation and that the surgery would be difficult — they might have to take out a piece of her stomach and move her esophagus

But her tumor had a mismatch repair mutation, so she joined the clinical trial. The first infusion was on Oct. 14 of that year. By January, her tumor was gone. Ms. Sideris has one side effect from the treatment — she needs to take medication now to improve how her adrenal glands function. But she says it is worth paying that price to avoid the onerous treatment that would have been in store for her.

“It’s been a journey,” she said. But, she added, she reasoned that she had nothing to lose when she agreed to try immunotherapy.

“I still had surgery as a backup if it didn’t work,” she said.