It was a small trial, with only 18 patients with rectal cancer, each of whom took the same medication.
But the results were amazing. Cancer disappeared in each patient, undetectable by physical examination, endoscopy, PET scans, or MRIs.
Dr. Luis A. Diaz Jr. of the Memorial Sloan Kettering Cancer Center, author of an article published Sunday in the New England Journal of Medicine describing the results, which were sponsored by the pharmaceutical company GlaxoSmithKline a cancer in every patient.
“I think this is the first time this has happened in the history of cancer,” Dr. Diaz said.
Dr. Alan P. Venook, a colorectal cancer specialist at the University of California, San Francisco who did not participate in the study, said he also thought he was the first.
A complete remission in each patient is “unheard of,” he said.
These patients with rectal cancer had undergone strenuous treatment: chemotherapy, radiation, and most likely life-altering surgery that could lead to bowel, urinary, and sexual dysfunction. Some would need colostomy bags.
They entered the study thinking that when it was over, they would have to undergo those procedures because no one really expected their tumors to go away.
But they were surprised: no more treatment was needed.
“There were many tears of happiness,” said Dr. Andrea Cercek, an oncologist at the Memorial Sloan Kettering Cancer Center and co-author of the paper, which was presented Sunday at the annual meeting of the American Society of Clinical Oncology.
Another surprise, Dr. Venook added, was that none of the patients had clinically significant complications.
On average, one in five patients has some form of adverse drug reaction such as that taken by patients, dostarlimab, known as a control point inhibitor. The drug was given every three weeks for six months and cost about $ 11,000 per dose. Unmasks cancer cells, allowing the immune system to identify and destroy them.
Although most adverse reactions are easily managed, between 3 and 5 percent of patients taking control point inhibitors have more serious complications that in some cases cause muscle weakness and difficulty swallowing and chewing.
The absence of significant side effects, Dr. Venook said, means that “either they didn’t treat enough patients or somehow these cancers are just different.”
In an editorial accompanying the paper, Dr. Hanna K. Sanoff of the University of North Carolina’s Lineberger Comprehensive Cancer Center, who did not participate in the study, described it as “small but compelling.” He added, however, that it is unclear whether the patients are cured.
“Very little is known about how long it takes to find out if a complete clinical response to dostarlimab is equivalent to a cure,” Dr. Sanoff told the editorial.
Dr. Kimmie Ng, a colorectal cancer expert at Harvard Medical School, said that while the results were “remarkable” and “unprecedented,” they should be replicated.
The inspiration for the study of rectal cancer comes from a clinical trial led in 2017 by Dr. Diaz funded by Merck, the pharmaceutical manufacturer. It involved 86 people with metastatic cancer that originated in various parts of their body. But all cancers shared a genetic mutation that prevented cells from repairing DNA damage. These mutations occur in 4% of all cancer patients.
Patients in this trial took a Merck control point inhibitor, pembrolizumab, for up to two years. Tumors shrank or stabilized by about a third in half of the patients and lived longer. Tumors disappeared in 10 percent of trial participants.
This led Dr. Cercek and Dr. Diaz to ask themselves: What if the drug was used long before in the course of the disease, before the cancer had a chance to spread?
They were decided by a study of patients with locally advanced rectal cancer: tumors that had spread to the rectum and sometimes to the lymph nodes, but not to other organs. Dr. Cercek had noticed that chemotherapy did not help some patients who had the same mutations that affected patients in the 2017 trial. Instead of shrinking during treatment, their rectal tumors grew. .
Perhaps, Dr. reasoned. Cercek and Dr. Diaz, immunotherapy with a checkpoint inhibitor would allow these patients to avoid chemotherapy, radiation, and surgery.
New developments in cancer research
Card 1 of 6
Progress in the field. In recent years, advances in research have changed the way cancer is treated. Here are some recent updates:
Pancreatic cancer. Researchers were able to tame advanced pancreatic cancer in a woman by genetically reprogramming her T cells, a type of white blood cell in the immune system, so that they could recognize and kill cancer cells. Another patient who received the same treatment did not survive.
Chemotherapy. There is a silent revolution in the field of cancer treatment: a growing number of patients, especially those with breast and lung cancer, are saving themselves from the dreaded treatment in favor of other options.
Leukemia. After receiving a new treatment, called CAR T cell therapy, more than a decade ago, two patients with chronic lymphocytic leukemia saw their blood cancer disappear. Their cases offer hope for people with the disease and create new mysteries.
Esophageal cancer. Nivolumab, an immune-releasing drug, has been found to prolong survival in patients with the disease who participated in a large clinical trial. Esophageal cancer is the seventh most common cancer in the world.
Dr. Diaz began asking companies that made checkpoint inhibitors if they would sponsor a small trial. He was dismissed, saying the trial was too risky. He and Dr. Cercek wanted to give the drug to patients who could be cured with standard treatments. What the researchers were proposing could end up allowing cancers to grow beyond the point where they could be cured.
“It’s very difficult to alter the standard of care,” Dr. Diaz said. “All standard care machinery wants to do surgery.”
Finally, a small biotech company, Tesaro, agreed to sponsor the study. Tesaro was bought by GlaxoSmithKline and Dr. Diaz said he had to remind the larger company they were doing the study: the company executives had virtually forgotten about the small trial.
His first patient was Sascha Roth, then 38 years old. She first noticed rectal bleeding in 2018, but otherwise felt good: she’s a runner and helps run a family-owned furniture store in Bethesda, Maryland.
During a sigmoidoscopy, he recalled, his gastroenterologist said, “Oh, no. I didn’t expect that!”
The next day, the doctor called Mrs. Roth. He had a tumor biopsy. “It’s definitely cancer,” he told her.
“I melted completely,” he said.
He was soon scheduled to start chemotherapy at Georgetown University, but a friend had insisted that he first see Dr. Philip Paty at the Sloan Kettering Memorial. Dr. Paty told him that he was almost certain that his cancer included the mutation that made him unlikely to respond well to chemotherapy. It turned out, however, that Mrs. Roth was eligible to enter the clinical trial. If I had started chemotherapy, I wouldn’t have done it.
I was not expecting a complete response to dostarlimab, Ms. Roth had planned to move to New York for radiation, chemotherapy, and possibly surgery after the trial ended. To preserve her fertility after the long-awaited radiation treatment, her ovaries were removed and put back under her ribs.
After the trial, Dr. Cercek broke the news to him.
“We looked at your scans,” he said. “There is absolutely no cancer.” He did not need any additional treatment.
“I told my family,” Mrs. Roth said. “They didn’t believe me.”
But two years later, he still has no trace of cancer.