It was a small trial with only 18 patients with rectal cancer, and they all took the same medication. But the results were astonishing. Cancer that disappeared in all patients became undetectable on physical examination, endoscopy, positron emission tomography (PET scan), and MRI.
Luis A. Diaz Jr., of the Memorial Sloan Kettering Cancer Center, describing the results of a study published Sunday in the New England Journal of Medicine, author of an article promoting the results of a study promoted by the pharmaceutical company GlaxoSmithKline, said he knew of no other research. in which a treatment completely eliminated the cancer of all patients.
“I think this is the first time this has happened in the history of cancer,” Diaz said.
Alan P. Venook, a colon cancer specialist at the University of California, San Francisco, who did not participate in the study, believes this was also the first case in history. The full remission of all patients is “unprecedented,” he said.
These cancer patients have undergone strenuous treatment: chemotherapy, radiation, and possibly surgery that can cause bowel, urinary, and sexual dysfunction. Some needed colostomy bags.
They went into the investigation thinking that they would have to undergo these procedures when they were finished, because no one really expected their tumors to go away. But they were surprised: no further treatment was needed.
“There were a lot of happy tears,” said Andrea Cerce, an oncologist at Memorial Sloan Kettering and co-author of the paper, who was presented Sunday at the American Society for Clinical Oncology for the annual meeting.
Another surprise, Venook added, was that one of the patients had no clinically significant complications. On average, 1 in 5 patients experience a adverse reaction to medication, such as that taken by patients, dostarlimab, known as an inhibitory control point.
The drug was given every three months for three weeks and cost about $ 11,000 per dose. It reveals cancer cells, allowing them to identify and destroy the immune system.
Although most adverse reactions are easily controlled, between 3% and 5% of patients taking point-inhibitors experience more serious complications, in some cases muscle weakness and difficulty swallowing and chewing.
In the absence of significant side effects, Venook said, “they haven’t treated enough patients or somehow these cancers are different.”
In an editorial accompanying the article, Hanna K. Sanoff of the Lineberger Cancer Center at the University of North Carolina, who did not participate in the study, said it was “small but interesting.” He added, however, that it was not clear whether the patients would be cured.
The inspiration for the cancer research came from a clinical trial led by Diaz in 2017, funded by the pharmaceutical company Merck. 86 people with cancer metastases from various parts of their bodies took part. 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 study took a Merck checkpoint inhibitor, pembrolizumab, for up to two years. Tumors were reduced or stabilized in one-third or one-half of patients, and they lived longer. The tumors disappeared in 10% of the study participants.
This led Cerce and Diaz to ask themselves: what would happen if the drug were used much earlier in the course of the disease before it could spread to cancer?
A study was conducted on patients with locally advanced cancer of the rectum: tumors that have spread to the rectum and sometimes to the lymph nodes, but not to other organs.
Cerce noted that chemotherapy did not help some patients with the same mutations that affected patients in the 2017 study. Instead of shrinking in treatment, rectal tumors grew.
Perhaps Cerce and Diaz argued that immunotherapy with a control point inhibitor would allow these patients to avoid chemotherapy, radiation, and surgery.
Diaz began by wondering if they would support a small lawsuit against companies that do inhibitory checkpoints. They refused, saying the examination was too dangerous. He and Cerce wanted to give the drug to patients who could be cured with standard treatments. What the researchers were proposing may allow the cancer to grow beyond the point where it can be cured.
“It’s very difficult to change the standard of care,” Diaz said. “The standard treatment is surgery.”
Finally, a small biotechnology company, Tesaro, agreed to support the research. Tesaro was bought by GlaxoSmithKline, and Diaz said he needed to remind the larger company that they were doing the test — the managers forgot about the small test.
Her first patient was Sascha Roth, then 38 years old. She first noticed a rectal bleeding in 2019, but she felt good: she’s a runner and helps run a family-owned furniture store in Bethesdan, Maryland.
In a sigmoidoscopy, his gastroenterologist said, “Oh, no. I didn’t expect that!”
The next day, the doctor called Roth. He had a tumor biopsy. “It’s definitely cancer,” he said.
“I was completely melted down,” he said.
He was soon ready to start chemotherapy at Georgetown University, but a friend pointed out that he would first see Dr. Philip Paty at Memorial Sloan Kettering.
Paty told him she was pretty sure her cancer included a mutation that was unlikely to make a good response to chemotherapy. However, it was demonstrated that Roth was eligible for admission to the clinical trial. If he had started chemotherapy, he would not have been able to.
Unexpectedly expecting a full response from Dostarlimab, Roth planned to travel to New York to undergo radiation, chemotherapy, and possibly surgery after the trial. He was expected to preserve fertility after radiation treatment, remove the ovaries and put them back under his ribs.
After the test, Cercek gave him the news.
“We’ve looked at your exams,” he said. “It’s not completely cancerous.” He did not need further treatment.
“I told my family,” Roth said. “They didn’t.”
Two years later, he has no trace of the disease.
Translated by Luiz Roberto M. Gonçalves