It was a small study, with just 18 rectal cancer patients, all of whom took the same drug.
However, the results were surprising. The cancer disappeared in all patients and was undetectable by physical examination, endoscopy, positron emission tomography (PET scans, as they are known), as well as MRIs.
Luis A. Diaz Jr., physician, Memorial Sloan Kettering Cancer Center, author of article posted on sunday In the New England Journal of Medicine detailing the results, sponsored by drugmaker GlaxoSmithKline, he said he was not aware of any other study in which a treatment had completely eliminated the cancer in all patients.
“I think this is the first time this has happened in the history of cancer,” Diaz said.
Alan P. Venook, a colorectal cancer specialist at the University of California, San Francisco, who was not involved in the study, said he also believed it was a first.
A complete remission in all patients is “unheard of,” he said.
These rectal cancer patients had the option of undergoing grueling treatments: chemotherapy, radiation therapy and, in most cases, life-altering surgery that might lead to bowel, urinary and sexual dysfunction. Some were going to need colostomy bags.
People entered the study thinking that when it was over, they would have to undergo those procedures because no one expected their tumors to go away.
But they got a surprise: no other treatment was necessary.
“There were a lot of happy tears,” recalled Andrea Cercek, an oncologist at Memorial Sloan Kettering Cancer Center and a co-author of the paper, which was presented Sunday at the annual meeting of the American Society of Clinical Oncology.
Another surprise, according to Venook, was that none of the patients had significant clinical complications.
On average, one in five patients has an adverse reaction to drugs like the one the patients took, dostarlimab, known as immune checkpoint inhibitors. The drug was given every three weeks for six months and cost regarding $11,000 per dose. This drug exposes cancer cells, allowing the immune system to identify and destroy them.
Although most adverse reactions are easily controlled, between three and five percent of patients taking checkpoint inhibitors develop more serious complications, in some cases causing muscle weakness and difficulty swallowing and chewing.
The absence of significant side effects, Venook said, means “either they didn’t treat enough patients or somehow these cancers are different.”
In a editorial Accompanying the article, Hanna K. Sanoff of the University of North Carolina Lineberger Comprehensive Cancer Center, who was not involved in the study, called it “small but compelling.” However, she added that it is not yet known if the patients are cured.
“Very little is known regarding the length of time needed to find out if a complete clinical response to dostarlimab equates to a cure,” Sanoff said in the editorial.
Kimmie Ng, a colorectal cancer oncologist at Harvard Medical School, said that while the results were “remarkable” and “unprecedented,” they would need to be replicated.
The inspiration for the rectal cancer study came from a clinical trial Diaz conducted in 2017, funded by pharmaceutical company Merck. That study involved 86 people with metastatic cancer in various parts of the body. But all cancers had in common a genetic mutation that prevented cells from repairing DNA damage. These mutations occur in four percent of cancer patients.
People in that trial took pembrolizumab, a checkpoint inhibitor made by Merck, for up to two years. The tumors shrank or stabilized in almost a third or even half of the patients and they lived longer. The tumors disappeared in 10 percent of the study participants.
That made Cercek and Diaz wonder what if the drug was used much earlier in the disease, before the cancer had a chance to spread?
They decided on a study of patients with locally advanced rectal cancer; that is, with tumors that had spread to the rectum and sometimes to the lymph nodes, but not to other organs. Cercek had noted that chemotherapy did not help a portion of people who had the same mutations that affected patients in the 2017 trial. Instead of shrinking during treatment, their rectal tumors grew.
Perhaps, Cercek and Diaz reasoned, immunotherapy with a checkpoint inhibitor would allow these patients to avoid treatments such as chemotherapy, radiation and surgery.
Diaz began asking companies that make checkpoint inhibitors if they might sponsor a small trial. Pharmaceuticals rejected it, arguing that the study was too risky. He and Cercek wanted to give the drug to patients who might be cured with standard treatments. What the researchers proposed might allow cancers to grow beyond the point where they were curable.
New Developments in Cancer Research
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“It is very difficult to alter the standard of care. The entire standard care machinery wants to do the surgery,” Diaz explained.
In the end, a small biotech company, Tesaro, agreed to sponsor the study. GlaxoSmithKline bought Tesaro and Diaz had to remind the larger company that they were doing the study; the executives had almost forgotten regarding the little essay.
His first patient was Sascha Roth, then 38 years old. The first time she noticed a rectal bleed was in 2019, but otherwise she felt fine; she is a broker and helps oversee a family furniture store in Bethesda, Maryland.
Roth recalled that during a sigmoidoscopy his gastroenterologist told him, “Oh no! I was not expecting this!”.
The next day, the doctor called. They had done a biopsy of the tumor. “It’s definitely cancer,” he told her.
“I felt dejected,” she said.
Roth was scheduled to start chemotherapy at Georgetown University shortly, but a friend had insisted that he first see Philip Paty, a physician at Memorial Sloan Kettering. Patty told him that he was almost certain that his cancer included the mutation that made it unlikely that he would respond well to chemotherapy. However, it turned out that Roth was eligible to participate in the clinical trial. If he had started chemotherapy, he would not have complied with them.
Not expecting a complete response to dostarlimab, Roth had planned to move to New York for radiation therapy, chemotherapy, and perhaps surgery following the trial was over. To preserve his fertility following the expected radiotherapy, her ovaries were removed and placed under her ribs.
After rehearsal, Cercek broke the news to him.
“We reviewed your studies,” he told her. “There is absolutely no cancer.” He didn’t need any more treatment.
“I told my family,” Roth said. “They didn’t believe me.”
But two years later, he still has no trace of cancer.
Gina Kolata writes regarding science and medicine. She is a two-time Pulitzer Prize finalist and the author of six books, including Mercies in Disguise: A Story of Hope, a Family’s Genetic Destiny, and The Science That Saved Them. @ginakolata