A Cancer Trial’s Unexpected Result: Remission in Every Patient

This was a small study, with only 18 patients with rectal cancer taking the same medication.

But the result was amazing. The cancer disappeared in all patients and could not be detected by physical examination, endoscopy, PET or MRI scans.

Dr. Lewis A. Diaz Jr., Memorial Sloan Kettering Cancer Center, paper Published Sunday in the New England Journal of Medicine, which explains the results sponsored by pharmaceutical company GlaxoSmithKline, he said he was unaware of other studies in which treatment completely eliminated cancer in all patients.

“I believe this is the first time this has happened in the history of cancer,” said Dr. Diaz.

Dr. Alan P. Benuk, a colorectal cancer specialist at the University of California, San Francisco, who was not involved in the study, also said he thought this was the first time.

He said complete remission in all patients was “unprecedented.”

These patients with colorectal cancer faced severe treatments such as chemotherapy, radiation therapy, and possibly life-changing surgery that could cause bowel, urine, and sexual dysfunction. Some people need an artificial anal bag.

They entered the study thinking that they would have to undergo those treatments because no one really expected their tumors to disappear when it was over.

But they were surprised. No further treatment was needed.

“There were many happy tears,” said Dr. Andrea Cercek, an oncology scholar at the Memorial Sloan Kettering Cancer Center and co-author of a paper presented Sunday at the American Society of Clinical Oncology’s annual meeting.

Another surprise is that Dr. Venook had no clinically significant complications in any of the patients.

On average, one in five patients have some side effects on what they take, drugs like dosterlimab, known as checkpoint inhibitors. The drug was given every 3 weeks for 6 months and cost about $ 11,000 per dose. It obscures cancer cells and allows the immune system to identify and destroy them.

Most side effects are easy to manage, but 3-5% of patients taking checkpoint inhibitors have more serious complications, and in some cases weakness, dysphagia, and chewing difficulties. Cause.

The absence of significant side effects means that “we did not treat a sufficient number of patients, or for some reason, these cancers are completely different.”

and editorial Accompanying the paper, Dr. Hannah K. Sanov of the University of North Carolina’s Rheinberger Center for Cancer Research, who was not involved in the study, called it “small but compelling.” However, she added that it was not clear if the patient had healed.

“Little is known about the time required to determine if a complete clinical response to Dosterlimab is equivalent to cure,” Dr. Sanov said in an editorial.

Dr. Kimmie Ng, an expert in colorectal cancer at Harvard Medical School, said the results were “notable” and “unprecedented” but needed to be reproduced.

The inspiration for rectal cancer research came from a clinical trial led by Dr. Diaz in 2017, funded by pharmaceutical company Merck. Eighty-six people with metastatic cancer that developed in different parts of the body were involved. However, all cancers shared genetic mutations that prevented cells from repairing damage to their DNA. These mutations occur in 4 percent of all cancer patients.

Patients in that study took pembrolizumab, a checkpoint inhibitor from Merck, for up to two years. Tumors shrank or stabilized and lived longer in about one-third to one-half of patients. Tumors disappeared in 10% of study participants.

Therefore, Dr. Cercek and Dr. Diaz asked: What if the drug was used in the early stages of the disease before the cancer spread?

They settled on a study of patients with locally advanced rectal cancer (a tumor that has spread to the rectum, sometimes to the lymph nodes, but not to other organs). Dr. Cercek found that chemotherapy did not help some patients with the same mutations that affected them in the 2017 trial. Instead of shrinking during treatment, their rectal tumors grew.

Perhaps Dr. Cercek and Dr. Diaz believed that immunotherapy with checkpoint inhibitors could avoid such patients from chemotherapy, radiation therapy, and surgery.

Dr. Diaz began asking companies that manufacture checkpoint inhibitors whether to sponsor a small trial. They turned him down, saying the trial was too dangerous. He and Dr. Cercek wanted to administer the drug to patients who could be cured with standard treatments. What the researchers have suggested may allow cancer to grow beyond what can be cured.

“It’s very difficult to change the standard of care,” said Dr. Diaz. “The entire standard of care machine wants to have surgery.”

Finally, a small biotechnology company, Tesaro, agreed to sponsor the research. Tesaro was acquired by GlaxoSmithKline, and Dr. Diaz said he needed to remind big companies that they were investigating. Business executives almost forgot about small trials.

Their first patient was Sascha Roth, who was 38 at the time. She first noticed rectal bleeding in 2018, but she was otherwise fine. She is a runner and helps run a home furniture store in Bethesda, Maryland.

During sigmoidoscopy, she remembered, her gastroenterologist said.Wasn’t me I’m expecting this! “

The next day, the doctor called Mr. Ross. He had a tumor biopsy. “It’s definitely cancer,” he told her.

“I’m completely melted,” she said.

Soon she was planning to start chemotherapy at Georgetown University, but a friend claimed she would meet Dr. Philip Patty first at Memorial Sloan Kettering. Dr. Patty told her she was almost certain that her cancer contained mutations that were unlikely to respond well to chemotherapy. However, Ross turned out to be eligible to participate in clinical trials. If she had started her chemotherapy, she wouldn’t.

Not expecting a complete response to Dosterlimab, Ross planned to move to New York for radiation therapy, chemotherapy, and perhaps post-study surgery.To maintain her fertility after the expected radiation therapy, she Her ovaries were removed and returned under the ribs..

After the trial, Dr. Sersek informed her.

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

“I talked to my family,” Ross said. “They didn’t believe me.”

But two years later, she still has no evidence of cancer.