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

A small drug trial is having a seismic impact in the world of oncology: After six months of an experimental treatment, tumors vanished in all 14 patients diagnosed with early-stage rectal cancer who completed the study by the time it was published.

Researchers in the field of colorectal cancer are hailing the study, published Sunday in the New England Journal of Medicine, as a groundbreaking development that could lead to new treatments for other cancers as well.

“I don’t think anyone has seen this before, where every single patient has had the tumor disappear,” said Andrea Cercek, an oncologist with 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 was given nine doses of intravenous dostarlimab, a relatively new drug designed to block a specific cancer cell protein that, when expressed, can cause the immune system to withhold its cancer-fighting response.

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

“All 14 patients? The odds are exceedingly low and really unheard of 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, nor did any have significant complications from the drug. Four other patients in the trial are still undergoing treatment but thus far are showing the same promising results.

Sascha Roth, the first patient to enter the experimental study in late 2019, knows firsthand how big a deal the results are, but said that since the news was released Sunday, she and her family are beginning to understand the broader impact.

“My cousin from Brussels said it’s in the paper there,” Roth said Tuesday. “It’s touching everybody.”

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

Though 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 can cause scarring of the uterus, making them unable to carry a pregnancy; other patients with low-situated rectal tumors need to permanently use a colostomy bag after surgery.

The study does have caveats: The sample size of patients, while diverse in age, race and ethnicity, was small. And even the earliest patients in the trial still have several more years of observation to ensure that the tumors haven’t reemerged or metastasized elsewhere in the body. The results also only pertain to those who carry specific abnormality to their rectal cancer known as mismatch repair-deficiency, which impedes the body’s function to normalize or “repair” abnormalities when cells divide and instead results in mutations. The deficiency occurs in roughly 5% to 10% of all rectal cancer patients and tends to resist chemotherapy.

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

David Ryan, the director of clinical oncology at Massachusetts General Hospital, said the results are a game changer for cancer patients with mismatch-repair deficiency. The study was sponsored by biotech company Tesaro—which was acquired by GlaxoSmithKline when the earliest patient began treatment in 2019.

“This is a very big deal,” said Ryan, who did not participate in the study. “It’ll be really hard not to think about this for the next patient who walks through the door: ‘Should I do chemo and radiation, or should I do this immunotherapy?’ ”

Ryan notes that the trial participants have and will continue to be closely monitored by a team of specialists who will be able to watch for any possible tumor recurrences or spread and quickly intervene with treatment if necessary. He said that necessity could be a challenge for patients who don’t live near where they can easily and regularly access care from specialists.

“We do worry that if recurrences happen, that they have to be picked up as soon as possible to give people the best chance,” he said.

But Ryan and Cercek separately said the trial results raise the specter that anyone with a mismatch repair deficiency in other tumor types, like 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 of cancer patients knowing their mismatch repair status.

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

Cercek presented the paper Sunday morning at the annual meeting of the American Society of Clinical Oncology in Chicago. She had not even finished her 10-minute presentation when the room broke into applause. Gasps and tears rippled through the audience as bold, white, underlined letters appeared on a blue screen with her study’s top-line finding: “100% clinical COMPLETE response in the first 14 consecutive patients.”

In layman’s terms, it was like spiking a football after a touchdown.

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

“All the stars aligned in a perfect way that allowed me to do this trial,” she said. “If I had done one infusion of chemo, that would have disqualified me.”

Roth, who lives in Bethesda, Md., and runs a furniture store, was diagnosed in September 2019 when she was 38 years old. She had experienced some rectal bleeding and chalked it up to the anti-inflammatories she took as a result of her active lifestyle that included the occasional bike crash and soccer collision.

“I thought they were going to tell me I had a gluten allergy,” Roth said. “I definitely was not anticipating 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 scheduled to begin chemotherapy in the Washington area, she met with a doctor at MSK who, she recalled, “threw down the gauntlet” in the exam room.

“He said, ‘One, you’re not a candidate for surgery because of where the cancer is located,'” and also advised her that chemotherapy—typically the standard care—would not be an effective option given that she had a cancer abnormality that tends to resist that treatment.

The doctor was near-certain she was a “Lynch” patient, or someone with an inherited cancer syndrome that’s 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 she could begin the experimental treatment.

“In my mind, every day that’s passing, I’m wide-eyed and crazy,” she said of the fear her cancer could worsen from Stage 3 to Stage 4 during the wait. “But I was reassured that cancer doesn’t grow in a day.”

Roth was closely monitored to ensure that it was safe to wait on treatment and keep her in the trial. She began the experimental therapy in December 2019. After her first infusion, she went to Florida on vacation and said she felt no adverse side-effects. She even continued running.

Halfway through the trial, Roth’s tumor was visibly shrinking. By the six-month mark, when Roth would transition to chemotherapy, she received a late Friday night call from Cercek telling her to cancel her move to New York. The researchers were going to adjust the trial; chemo—along with radiation or surgery—would no longer be necessary, at least for now.

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

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

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