This was a small trial, just 18 patients with rectal cancer, all of whom were taking the same drug.
But the results were amazing. The cancer disappeared in each patient, undetectable by physical examination, endoscopy, PET or MRI.
Dr. Luis A. Diaz Jr. of 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 pharmaceutical company GlaxoSmithKline, said he was unaware no other study in which one treatment completely erased cancer in every patient.
“I believe 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 was not involved in the study, said he also thought it was a first.
Complete remission in every patient is “unprecedented,” he said.
These rectal cancer patients had faced grueling treatments – chemotherapy, radiation and, most likely, life-changing 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 these procedures because no one really expected their tumors to go away.
But they got a surprise: no further treatment was needed.
“There were a lot of tears of joy,” said Dr. Andrea Cercek, an oncologist at Memorial Sloan Kettering Cancer Center and co-author of the paper, which was presented Sunday at the American Society’s annual meeting. of Clinical Oncology.
Another surprise, Dr. Venook added, was that none of the patients had clinically significant complications.
On average, one in five patients have some sort of adverse reaction to drugs like the one the patients took, dostarlimab, known as checkpoint inhibitors. The drug was given every three weeks for six months and cost around $11,000 per dose. It unmasks cancer cells, allowing the immune system to identify and destroy them.
While most side effects are easily managed, up to 3-5% of patients taking checkpoint inhibitors have more serious complications, which in some cases result in muscle weakness and difficulty swallowing and to chew.
The lack of significant side effects, Dr. Venook said, means “either they haven’t treated enough patients or somehow these cancers are just different” .
In an editorial accompanying the article, Dr. Hanna K. Sanoff of the University of North Carolina’s Lineberger Comprehensive Cancer Center, who was not involved in the study, called it “small but compelling.” She added, however, that it is unclear whether the patients are cured.
“Very little is known about how long it takes to know if a complete clinical response to dostarlimab equates to a cure,” Dr. Sanoff said in the editorial.
Dr Kimmie Ng, a colorectal cancer expert at Harvard Medical School, said while the results were “remarkable” and “unprecedented” they should be replicated.
The inspiration for the rectal cancer study came from a clinical trial Dr. Diaz conducted in 2017 and funded by Merck, the drugmaker. It involved 86 people with metastatic cancer originating in various parts of their bodies. But the cancers all 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 checkpoint inhibitor, pembrolizumab, for up to two years. Tumors shrank or stabilized in about one-third to one-half of patients, and they lived longer. Tumors disappeared in 10% of trial participants.
This caused Dr. Cercek and Dr. Diaz to wonder: what if the drug was used much earlier in the course of the disease, before the cancer had a chance to spread?
They opted for a study of patients with locally advanced rectal cancer – tumors that had spread to the rectum and sometimes to lymph nodes, but not to other organs. Dr. Cercek had noticed that chemotherapy was not helping a portion of patients who had the same mutations that affected patients in the 2017 trial. Instead of shrinking during treatment, their rectal tumors grew.
According to Dr. Cercek and Dr. Diaz, immunotherapy with a checkpoint inhibitor may allow these patients to avoid chemotherapy, radiation therapy and surgery.
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Dr. Diaz began asking companies that made checkpoint inhibitors if they would sponsor a small trial. They refused it, 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 change the standard of care,” Dr. Diaz said. “All the standard care machinery wants to do the surgery.”
Finally, a small biotechnology company, Tesaro, agreed to sponsor the study. Tesaro was bought by GlaxoSmithKline, and Dr Diaz said he needed to remind the larger company they were running the study – company executives had all but forgotten about the small trial.
Their first patient was Sascha Roth, then 38 years old. She first noticed rectal bleeding in 2019, but otherwise felt fine — she’s a runner and helps run a family-owned furniture store in Bethesda, Maryland.
During a sigmoidoscopy, she recalls, her gastroenterologist said, “Oh no. I was not I expected that!”
The next day, the doctor called Mrs. Roth. He had undergone a biopsy of the tumor. “It’s definitely cancer,” he told her.
“I completely melted,” she said.
Soon she was due to start chemotherapy at Georgetown University, but a friend had insisted she first see Dr Philip Paty at Memorial Sloan Kettering. Dr. Paty told him that he was almost certain that his cancer included the mutation that prevented him from responding well to chemotherapy. It turned out, however, that Ms Roth was eligible to take part in the clinical trial. If she had started chemotherapy, she wouldn’t have been.
Not expecting a full 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 scheduled radiation therapy, she had her ovaries removed and put back under her ribs.
After the trial, Dr. Cercek broke the news to him.
“We looked at your scans,” she said. “There is absolutely no cancer.” She did not need any further treatment.
“I told my family,” Ms Roth said. “They didn’t believe me.”
But two years later, she still has no trace of cancer.