“I don’t think anyone has seen this before where the tumor has gone away in every single patient,” said Andrea Cercek, an oncologist at Memorial Sloan Kettering Cancer Center in New York and lead author of the study.
The patients all had the same genetic instability of their rectal cancer and had not been treated before. Each received nine doses of dostarlimab intravenously, 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 nodular, discolored tumors showed smooth, pinkish tissue instead. No trace of cancer was found on scans, biopsies, or physical examinations.
“All 14 patients? The odds are extremely slim and truly unheard of in oncology,” said Cercek.
The results were so successful that none of the 14 patients who completed the study required the planned follow-up treatment of chemotherapy or surgery, nor had any significant complications from the drug. Four other patients in the study are still being treated but are showing the same promising results so far.
Sascha Roth, the first patient enrolled in the experimental study in late 2019, knows firsthand the magnitude of the findings but said she and her family are beginning to understand since the news was published on Sunday the broad effect.
“My cousin from Brussels said it was in the newspaper there,” Roth said on Tuesday. “It touches everyone.”
The results point to a promising option for treating rectal cancer, which can often have life-changing effects in patients.
Although rectal cancer is highly survivable in its early stages, the most effective traditional treatments such as radiation, chemotherapy and surgery can also result in patients with permanent bowel and bladder dysfunction, sexual dysfunction and infertility. In younger women, the treatment can cause scarring of the uterus, making them unable to carry a child to term; other patients with low-lying rectum tumors need to use a colostomy bag permanently after surgery.
The study has caveats: the sample size of patients, while varied in age, race, and ethnicity, was small. And even the earliest patients in the study have several years of follow-up to make sure the tumors haven’t come back or metastasized elsewhere in the body. The findings also only apply to those who carry a specific abnormality of their rectal cancer, known as mismatch repair deficiency, which interferes with the body’s ability to normalize, or “repair,” abnormalities when cells divide and cause mutations instead leads. The deficiency occurs in about 5 to 10 percent of all rectal cancer patients and tends to resist chemotherapy.
“We’re definitely seeing an influx of callers saying, ‘Is this drug for me?’ ‘ Cercek said. “It’s a very emotional reaction of, ‘Oh my god, they had cancer and now look at them.’ ”
David Ryan, director of clinical oncology at Massachusetts General Hospital, said the results are a game changer for mismatch-repair-deficient cancer patients. The study was sponsored by biotech company Tesaro, which was acquired by GlaxoSmithKline when the first patient started treatment in 2019.
“This is a very big deal,” said Ryan, who did not take part in the study. “It’s going to be really hard for the next patient that walks in the door not to be thinking, ‘Should I do chemo and radiation or should I do this immunotherapy?’ ”
Ryan said study participants have been and will be closely monitored by a team of specialists who will be able to monitor for possible tumor recurrence or spread and quickly intervene with treatment if necessary. He said the need could be a challenge for patients who don’t live nearby where they can easily and regularly access specialist care.
“We’re concerned that recurrences need to be fixed as soon as possible to give people the best chance,” he said.
But Ryan and Cercek said separately that the study results raise the specter that anyone with a mismatch repair deficiency in other tumor types, 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 underscores the importance of cancer patients knowing their mismatch repair status.
“We always knew about this, but we didn’t know that these are the types of tumors that respond like gangsters to immunotherapy and the tumors melt 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 finished her 10-minute presentation when the room erupted in applause. Gasps and tears ran through the audience as bold, white, underlined letters appeared on a blue screen with the key finding of their study: “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, is feeling equally triumphant. She described her path into the process as “bizarre”.
“All the stars were perfectly aligned, which allowed me to do this test,” she said. “Had I done a chemo infusion, that would have disqualified me.”
Roth, who lives in Bethesda, Maryland and runs a furniture store, was diagnosed in September 2019 at the age of 38. She had suffered some rectal bleeding and attributed it to the anti-inflammatory drugs she was taking due to her active lifestyle, which included occasional bike accidents and soccer ball collisions.
“I thought they were going to tell me I had a gluten allergy,” Roth said. “I definitely wasn’t expecting a cancer diagnosis.”
She spoke to a friend who had been diagnosed with colon 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 with a doctor at MSK who she recalled “running the gauntlet” in the exam room.
“He said, ‘First, you’re not a candidate for surgery because the cancer is there,'” also advising her that chemotherapy — usually the standard of care — wouldn’t be an effective option since she had a cancerous abnormality that tended to to withstand this treatment.
The doctor was pretty sure 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 study’s first patient.
Roth had to wait another two months for FDA approval before she could begin the experimental treatment.
“In my mind, every day that goes by, I’m wide-eyed and crazy,” she said of fears that her cancer might worsen from stage 3 to stage 4 during the wait. “But I’ve been assured that cancer doesn’t grow in a day.”
Roth was closely monitored to ensure it was safe to await treatment and keep her in the study. She began the experimental therapy in December 2019. After her first infusion, she went on vacation to Florida and said she felt no side effects. She even kept walking.
Halfway through the study, Roth’s tumor visibly shrank. After six months, when Roth would be moving on to chemotherapy, she received a call from Cercek late Friday night telling her to cancel her move to New York. The researchers would adapt the process; Chemo – together with radiation or surgery – would no longer be necessary, at least for the time being.
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 those who encouraged them to stand up for themselves and get a second opinion.
Given the prevalence of cancer in her family, she is also grateful for the advances in science. Roth’s father died of brain cancer in 1999, and her mother is currently “in the last days of her life” battling cancer. Thanks to the innovations in this field, she is optimistic about her own future.
“I feel a universal sense of gratitude — but hope for others, too,” she said. “Hope for all cancers.”