Cancer study surprises with disease remission in all patients

It was a small trial, with just 18 patients with rectal cancer, and they all took the same drug. But the results were surprising. The cancer disappeared in all patients, becoming undetectable on physical examinations, endoscopy, positron emission tomography (PET scans) and MRI.

Luis A. Diaz Jr., of Memorial Sloan Kettering Cancer Center, author of a paper published Sunday in the New England Journal of Medicine describing the results of the study, which was sponsored by the pharmaceutical company GlaxoSmithKline, said he knew of no other study in which one treatment completely obliterated the cancer in all patients.

“I believe 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 thinks this was the first case in history. Complete remission in all patients is “unprecedented,” he said.

These rectal cancer patients have faced grueling treatments — chemotherapy, radiation and, most likely, surgery that can result in bowel, urinary and sexual dysfunction. Some needed 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 were in for a surprise: no further treatment was needed.

“There were a lot of tears of happiness,” said Andrea Cercek, an oncologist at Memorial Sloan Kettering and co-author of the paper, which was presented Sunday at the annual meeting of the American Society for Clinical Oncology.

Another surprise, Venook added, was that none of the patients had clinically significant complications. On average, 1 in 5 patients has some kind of adverse reaction to drugs like what the patients took, dostarlimab, known as checkpoint inhibitors.

The medication was given every three weeks for six months and cost about $11,000 per dose. It unmasks cancer cells, allowing the immune system to identify and destroy them.

Although most adverse reactions are easily controlled, approximately 3% to 5% of patients taking checkpoint inhibitors experience more serious complications that, in some cases, result in muscle weakness and difficulty swallowing and chewing.

The absence of significant side effects, Venook said, means “either they haven’t treated enough patients, or somehow these cancers are just different.”

In an editorial accompanying the article, 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 interesting.” She added, however, that it is unclear whether the patients are cured.

The inspiration for the rectal cancer study came from a clinical trial Diaz led in 2017, funded by pharmaceutical company Merck. It involved 86 people with metastatic cancer that originated in various parts of their bodies. 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 shrank or stabilized in about one-third to one-half of patients, and they lived longer. Tumors disappeared in 10% of study participants.

This led Cercek and Diaz to ask themselves: what would happen if the drug was used much earlier in the course of the disease, before the cancer had a chance to spread?

They settled on a study of patients with locally advanced rectal cancer — tumors that have spread to the rectum and sometimes to the lymph nodes but not to other organs.

Cercek had noticed that the chemotherapy was not helping some of the patients who had the same mutations that affected the patients in the 2017 study. 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 chemotherapy, radiation and surgery.

Diaz began asking companies that made checkpoint inhibitors if they would sponsor a small trial. They declined, saying the study was too risky. He and Cercek wanted to give the drug to patients who could be cured with standard treatments. What the researchers were proposing could allow cancers to grow beyond the point where they can be cured.

“It’s very difficult to change the standard of care,” Diaz said. “Standard treatment is to have surgery.”

Finally, a small biotechnology company, Tesaro, agreed to sponsor the study. Tesaro was bought by GlaxoSmithKline, and Diaz said he had to remind the larger company that they were doing the study — the executives had forgotten about the little test.

His first patient was Sascha Roth, then 38 years old. She first noticed some rectal bleeding in 2019, but she felt fine — she’s a runner and helps run a family furniture store in Bethesda, Maryland.

During a sigmoidoscopy, she recalled, her gastroenterologist said, “Oh no. I didn’t expect that!”

The next day, the doctor called Roth. He had taken a biopsy of the tumor. “It’s definitely cancer,” he said.

“I completely melted,” she said.

Soon she was ready to begin chemotherapy at Georgetown University, but a friend insisted that she see Dr Philip Paty at Memorial Sloan Kettering first.

Paty told her that she was pretty sure her cancer included the mutation that made a good response to chemotherapy unlikely. It turned out, however, that Roth was eligible to enter the clinical trial. If she had started chemotherapy, she couldn’t.

Not expecting a complete response to dostarlimab, Roth had planned to move to New York for radiation, chemotherapy and possibly surgery after the trial was over. To preserve her fertility after the expected radiation treatment, she had her ovaries removed and placed back under her ribs.

After the test, Cercek broke the news to him.

“We’ve analyzed your scans,” she said. “There is absolutely no cancer.” She didn’t need any further treatment.

“I told my family,” Roth said. “They didn’t.”

Two years later, she has no trace of the disease.

^{Translated by Luiz Roberto M. Gonçalves}