Small rectal cancer drug trial sees tumors disappear in 100% of patients

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Small drug trial has seismic impact in oncology world: After six months of experimental treatment, tumors disappeared in 14 patients diagnosed with early-stage rectal cancer who completed study at the time of its publication.

Colorectal cancer researchers hail the study, published Sunday in the New England Journal of Medicine, as a groundbreaking development that could also lead to new treatments for other cancers.

“I don’t think anyone has seen this before, where every patient has seen their tumor disappear,” said Andrea Cercek, an oncologist at Memorial Sloan Kettering Cancer Center in New York and lead author of the study.

The patients all shared the same genetic instability in their rectal cancer and had not yet undergone treatment. Each received nine doses of intravenous dostarlimab, a relatively new drug designed to block a cancer cell-specific protein that, when expressed, can cause the immune system to withhold its anti-cancer response.

After six months, scans that once showed lumpy, discolored tumors instead revealed smooth, pink tissue. No trace of cancer was detected in scans, biopsies or physical exams.

“All 14 patients? The odds are extremely low and really unknown in oncology,” Cercek said.

The results were so successful that none of the 14 patients who completed the trial needed the planned follow-up treatment of chemo-radiation or surgery, and none had significant complications from the drug. . Four other patients in the trial are still on treatment but are showing the same promising results so far.

Sascha Roth, the first patient to enter the experimental study in late 2019, knows firsthand how important the results are, but said that since the news broke on Sunday, she and her family are beginning to understand. the wider impact.

“My cousin from Brussels said it was in the paper there,” Roth said Tuesday. “It affects everyone.”

The results point to a promising option for the treatment of rectal cancer, which can often leave patients with life-changing effects.

Although rectal cancer is highly survivable when treated in its early stages, the most effective traditional treatments of radiation, chemotherapy, and surgery can also leave patients with permanent bowel and bladder dysfunction. sexual dysfunction and infertility. For younger women, the treatment may cause scarring of the uterus, rendering them unable to carry a pregnancy; other patients with low rectal tumors must permanently use a colostomy bag after surgery.

The study has caveats: The sample size of patients, while diverse in terms of age, race and ethnicity, was small. And even the first patients in the trial still have several years of observation to make sure the tumors haven’t reappeared or metastasized elsewhere in the body. The results also apply only to those who carry a specific abnormality in their rectal cancer known as mismatch repair deficit, which prevents the body’s function from normalizing or “repairing” abnormalities when cells divide and instead lead to mutations. The deficiency occurs in about 5-10% of all rectal cancer patients and tends to be resistant to chemotherapy.

“We’re definitely seeing an influx of people calling in saying, ‘Is this drug for me? “said Cercek. “It’s a very emotional reaction of, ‘Oh my God, they had cancer and now look at them.’ ”

Scott Gottlieb, Commissioner of the U.S. Food and Drug Administration, details the steps the U.S. government is taking to approve innovative new cancer drugs, therapies, and clinical trials. (Video: Washington Post Live)

David Ryan, director of clinical oncology at Massachusetts General Hospital, said the findings were a game-changer for cancer patients with a mismatch repair deficit. The study was sponsored by biotech company Tesaro – which was acquired by GlaxoSmithKline when the first patient started treatment in 2019.

“It’s a really big deal,” said Ryan, who wasn’t involved in the study. “It’s going to be really hard not to think about it for the next patient that comes through the door: ‘Should I do chemo and radiation, or should I do this immunotherapy?’ ”

Ryan said trial participants have been and will continue to be closely monitored by a team of specialists who will be able to watch for any recurrence or spread of the tumor and intervene quickly with treatment if needed. He said the need could be a challenge for patients who don’t live near a place where they can easily and regularly access specialist care.

“We are concerned that if recurrences occur they should be caught as soon as possible to give people the best chance,” he said.

But Ryan and Cercek said separately that the trial results raise the specter that anyone with a mismatch repair deficit in other types of tumors, such as those of the pancreas, stomach or bladder , could be effectively treated with the same drug from Cercek’s study.

For Ryan, the study also reinforces the importance for cancer patients to know their mismatch repair status.

“We always knew that, but we didn’t know that these were the types of tumors that respond like gangbusters to immunotherapy and tumors melt away like butter with treatment,” he said. .

Cercek presented the paper Sunday at the American Society of Clinical Oncology annual meeting in Chicago. She hadn’t even finished her 10-minute presentation when the room erupted in applause. Gasps and tears ran through the audience as bold underlined white letters appeared on a blue screen with the key finding of his study: “100% COMPLETE clinical response in the first 14 consecutive patients”.

Simply put, it was like kicking a football after a touchdown.

Roth, now 41, feels equally triumphant. She described her journey through the trial as “bizarre”.

“All the stars lined up perfectly, which allowed me to do this test,” she said. “If I had done just one chemo infusion, it would have disqualified me.”

Roth, who lives in Bethesda, Maryland, and runs a furniture store, was diagnosed in September 2019 when she was 38. She had had rectal bleeding and attributed it to anti-inflammatories she had been taking due to her active lifestyle, which included occasional bicycle accidents and football collisions.

“I thought they were going to tell me I had a gluten allergy,” Roth said. “I certainly wasn’t expecting a cancer diagnosis.”

She spoke to a friend who had been diagnosed with colorectal cancer a year and a half earlier who advised her: Memorial Sloane Kettering or bust. Three days before she was due to start chemotherapy in the Washington area, she met an MSK doctor who she recalled “throwing down the gauntlet” in the exam room.

“He said, ‘One, you’re not a candidate for surgery because of where the cancer is'” and also informed her that chemotherapy – usually standard care – would not be a an effective option given that she had a cancerous abnormality that tends to be resistant to this treatment.

The doctor was almost certain that she was a “Lynch” patient, or someone with an inherited cancer syndrome associated with abnormalities. Roth’s doctor introduced her to Cercek, and she soon became the trial’s first patient.

Roth would have to wait another two months for FDA approval before he could start the experimental treatment.

“In my mind, with each passing day, I’m wide-eyed and insane,” she said of fearing her cancer could worsen from stage 3 to stage 4 while waiting. . “But I was reassured that cancer does not develop overnight.”

Roth was closely watched to make sure it was safe to wait for her treatment and keep her in the trial. She started the experimental therapy in December 2019. After her first infusion, she went on vacation to Florida and reported experiencing no adverse side effects. She even continued to run.

Halfway through the trial, Roth’s tumor was visibly shrinking. After six months, when Roth switched to chemotherapy, she received a call late Friday night from Cercek telling her to cancel her move to New York. The researchers would adjust the trial; chemo – as well as radiation or surgery – would no longer be necessary, at least for now.

Roth’s family jokes that she is a “unicorn”, a living example of a medical miracle. What Roth feels is gratitude — for the doctors and nurses, and for those who encouraged her to stand up for herself and seek a second opinion.

She is also grateful for scientific advances, given the prevalence of cancer in her family. Roth’s father died of brain cancer in 1999, and his mother is currently living “the last days of her life” battling cancer. Thanks to innovations in the field, she feels optimistic about her own future.

“I feel a universal sense of gratitude – but also of hope for others,” she said. “Hope for all cancers.”

About Hector Hedgepeth

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