Unexpected Outcome of a Cancer Trial: Forgiveness in each patient

It was a small trial, with only 18 rectal cancer patients, each taking the same medication.

But the results were surprising. The cancer has disappeared in every patient, cannot be detected by physical examination, endoscopy, PET scan or MRI scan.

Dr. Lewis A. of Memorial Sloan Kettering Cancer Center. Diaz Jr., author of a study published Sunday in the New England Journal of Medicine, which described the results, which was sponsored by the drug company GlaxoSmithKline, said he did not know of any other research. Which is a treatment that completely eliminates cancer in every patient.

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

A colorectal cancer specialist at the University of California, San Francisco. Alan P. Venuk, who was not involved in the study, said he thought it was the first time.

The complete remission of each single patient is “tearless,” he said.

Patients with this rectal cancer have undergone difficult treatment – chemotherapy, radiation and, possibly, life-changing surgery that can lead to bowel, urination and sexual dysfunction. Some colostomy bags will be needed.

They entered the study thinking that once it was over, they would have to do those procedures because no one expected their tumors to disappear.

But they were surprised: no more treatment was needed.

“There were tears of joy,” said Dr. Andrea Cerseck, a cancer specialist at Memorial Sloan Kettering Cancer Center and co-author of the paper, which was presented at the annual meeting of the American Society of Clinical Oncology on Sunday.

Another surprise, Dr. Venuk added, was that none of the patients had clinically significant complications.

On average, one out of every five patients has some kind of adverse reaction to a drug such as the one that patients take, known as dosterlimab, a checkpoint inhibitor. The drug was given every three weeks for six months and cost about $ 11,000 per dose. It unmasks cancer cells, allowing the immune system to detect and destroy them.

Although most adverse reactions are easily managed, about 3 percent to 5 percent of patients who take checkpoint inhibitors have more serious complications that in some cases cause muscle weakness and difficulty swallowing and chewing.

The absence of significant side effects, Dr. Venuk said, means that “either they have not treated enough patients or, somehow, these cancers are quite different.”

In an editorial accompanying the research paper, Dr. Hannah K. of the Leinberger Comprehensive Cancer Center at the University of North Carolina. Sanaf, who was not involved in the study, called it “small but compelling.” He added, however, that it was not clear whether the patients had recovered.

“Little is known about the time required to find out whether the clinical complete response to dosterlimab is equivalent to cure,” Dr. Sanof said in an editorial.

Dr Kimi Ng, a colorectal cancer specialist at Harvard Medical School, said the results were “significant” and “unprecedented” but needed to be replicated.

The inspiration for the rectal cancer study came in 2017 from a clinical trial led by Dr. Diaz, funded by drug manufacturer Mark. It involved 86 people with metastatic cancer that developed in different parts of their bodies. But cancer all share a gene mutation that prevents cells from repairing DNA damage. These mutations occur in up to 4 percent of all cancer patients.

In that trial, patients took a mark checkpoint inhibitor, pembrolizumab, for up to two years. Tumors shrink or stabilize in about one-third to one-half of patients, and they survive longer. Tumors have disappeared in 10 percent of trial participants.

This prompted Dr. Ceresque and Dr. Diaz to ask: What if the drug was used long before the disease spread, before the cancer had spread?

They settled on a study on patients with locally advanced rectal cancer – tumors that spread to the rectum and sometimes to the lymph nodes but not to other organs. Dr. Ceresek noted that chemotherapy was not helping a portion of patients who had the same mutations that affected patients in the 2017 trial. Their rectal tumors grow instead of shrinking during treatment.

Presumably, Dr. Seresek and Dr. Diaz argued that immunotherapy with a checkpoint inhibitor would allow such patients to avoid chemotherapy, radiation, and surgery.

Dr. Diaz began asking companies that make checkpoint inhibitors if they would sponsor a small trial. They rejected him, saying the trial was too risky. He and Dr. Seresek wanted to give this medicine to patients who could be cured by quality treatment. What the researchers were proposing was to finally let the cancer go beyond the point where it could be cured.

“It’s very difficult to change the quality of care,” said Dr. Diaz. “The whole standard-of-care device wants surgery.”

Eventually, a small biotechnology firm, Tesaro, agreed to sponsor the study. Tessaro was bought by GlaxoSmithKline, and Dr. Diaz said he had to remind the big company that they were studying – the company’s executives had forgotten about the small trial.

Their first patient was Sascha Roth, then 38 years old. He first noticed some rectal bleeding in 2018 but felt better otherwise – he was a runner and helped run a family furniture store in Bethesda, Md.

During a sigmoidoscopy, he recalled, his gastroenterologist said, “Oh no. I wasn’t. I hope so! “

The next day, the doctor called Mrs. Roth. Her tumor was biopsied. “It’s definitely cancer,” he told her.

“I completely melted,” he said.

Soon, he was scheduled to begin chemotherapy at Georgetown University, but a friend insisted that he first study medicine at Memorial Sloan Catering. See Philip Patty. Dr. Patty told him that he was almost certain that his cancer involved mutations that were unlikely to respond well to chemotherapy. It turned out, however, that Mrs. Roth was eligible for entry into the clinical trial. If he had started chemotherapy he would not have been.

Without expecting a full response from Dusterlimab, Mrs. Roth planned to travel to New York for radiation, chemotherapy and possibly surgery after the trial was over. To preserve her fertility after the expected radiation treatment, her ovaries were removed and placed under her ribs.

After the trial, Dr. Sarsek informed him.

“We saw your scan,” he said. “No cancer.” He did not need any further treatment.

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

But even after two years, there is no sign of her cancer.

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