A small clinical trial has a seismic impact on the world of oncology: after six months of experimental treatment, tumors disappeared in all 14 patients diagnosed with early-stage rectal cancer who participated in the study from the date of publication.
Researchers in the field of colorectal cancer point to a study published Sunday in a scientific journal New England Journal of Medicineas a revolutionary discovery that could pave the way for new treatments for other cancers.
“I don’t think anyone has seen this before, where every patient has seen the tumor disappear,” said Andrea Cerkek, an oncologist at the Sloan Kettering Cancer Memorial Center in New York and lead author of the study.
All patients with rectal cancer they shared the same genetic instability and had not yet undergone treatment. Each received nine doses of intravenous dostarlimab, a relatively recent drug designed to block a specific cancer cell protein, which, when expressed, can cause the immune system to suspend its response in the fight against cancer.
After six months, images that once showed lumpy, altered tumors instead revealed smooth, pink tissue. Examinations, biopsies or physical examinations did not reveal any signs of cancer.
“All 14 patients? The chances are extremely low and really unheard of in oncology “, says Andrea Čerček.
The results were so successful that none of the 14 patients who completed the clinical trial required the next planned treatment with chemotherapy, radiation, or surgery. Also, no patient had significant complications after taking the drug. Four other patients in the clinical trial are still in treatment, but so far show the same promising results.
Sascha Roth, the first patient to enter the experimental study in late 2019, knows first hand how important the results are, but says that since the news was released on Sunday, she and her family are beginning to realize that the study had a wider impact.
“My cousin from Brussels said it was in the newspapers there,” he explains. Sasha Roth. “It impresses everyone.”
The results indicate a promising option in the treatment of rectal cancer, which can often leave patients with life-threatening consequences.
Although rectal cancer has a high survival rate when treated in its early stages, more effective traditional radiation treatments, chemotherapy and surgery can also leave patients with permanent bowel and bladder dysfunction, sexual dysfunction and infertility. For younger women, the treatment can leave scars on the uterus, making them unable to conceive; depending on the location of the rectal tumor, other patients may need to carry a colostomy bag permanently after surgery.
But the study has some caveats: the size of the patient’s sample, although different in age and ethnicity, was small. Even the first patients to participate in a clinical trial still have several years of observation ahead of them to ensure that tumors do not recur or metastasize elsewhere in the body. The results also apply only to those who have a specific rectal cancer abnormality that corresponds to a lack of DNA repair mechanisms, which prevents the body from normalizing or “correcting” abnormalities when cells divide, and instead results in mutations. This abnormality occurs in about 5 to 10% of all patients with rectal cancer and tends to resist chemotherapy.
“We definitely see an influx of people calling and asking, ‘Is this drug good for me?'” Cercek said. “It’s a very emotional reaction: ‘Oh my God, they had cancer and look at them now.'”
“Tumors melt like butter with this treatment”
David Ryan, director of clinical oncology at Massachusetts General Hospital, points out that the results are critical for cancer patients who have this specific anomaly. The study was sponsored by biotechnology company Tesaro – which was bought by GlaxoSmithKline when the first patient began treatment in 2019.
“This is very important,” says Ryan, who was not involved in the study. “It will be very difficult for the next patient who walks in the door not to think about this option: ‘Should I get chemotherapy and radiation or should I get this immunotherapy?’
Ryan notes that participants in the clinical trial will continue to be closely monitored by a team of experts who will be able to observe possible tumor recurrences or their spread and intervene quickly with treatment if necessary. The oncologist also explains that patients who do not live near a place where they can easily and regularly access specialist health care can face a challenge.
“We are concerned that if relapses occur, they must be detected as soon as possible in order to give people a better chance,” he added.
But Ryan and Cercek agree that the results of a clinical trial increase the possibility that anyone with abnormalities in DNA repair mechanisms in other types of tumors, such as pancreatic, gastric or bladder tumors, can be effectively treated with the same drug as the Cercek study.
For Ryan, the study also emphasizes the importance of knowing the clinical status and tumor type of cancer patients. “We always knew that, but we didn’t know that these are the types of tumors that respond effectively to immunotherapy and that tumors melt like butter with this treatment,” he says.
“All the stars are aligned”
Cercek presented the paper Sunday at the annual meeting of the American Society of Clinical Oncology in Chicago. She did not even finish her ten-minute presentation when the room began to applaud. Sighs and tears flooded the audience as bold, white, underlined letters appeared on the blue screen with the key finding of their study: “100% COMPLETE clinical response in the first 14 consecutive patients.” In layman’s terms, it was like making a touchdown.
Sasha Roth, now 41, feels equally triumphant. The woman describes her journey during clinical classes as “bizarre”. “All the stars lined up in a perfect way, which allowed me to participate in this clinical trial,” he explains. “If I had received a chemotherapy infusion, it would have disqualified me.”
Roth, who lives in Bethesda, Maryland and owns a furniture store, was diagnosed in September 2019, when he was 38 years old. He had rectal bleeding and blamed anti-inflammatory drugs for his active lifestyle, which included occasional bicycle accidents and a run into football.
“I thought he was going to tell me I had a gluten allergy,” Roth says. “I definitely didn’t expect a cancer diagnosis.”
The woman spoke to a friend who had been diagnosed with colorectal cancer a year and a half earlier, who advised her: Memorial Sloan Kettering Cancer Center. Three days before the start of chemotherapy in the Washington area, he met with a doctor at the Sloan Kettering Cancer Memorial Center, who, he recalls, “threw a glove on the floor” in the examination room.
He said, “First of all, she is not a candidate for surgery because of the location of the cancer,” and he also advised her that chemotherapy – a common treatment – would not be an effective option, given that she had cancer. an abnormality that tends to resist this treatment.
The doctor was almost certain that Roth would be a patient with Lynch syndrome or someone with a hereditary cancer syndrome associated with abnormalities. Roth’s doctor introduced her to Cercek and she soon became the first patient in a clinical trial.
gratitude and hope
Sasha Roth would have to wait another two months for approval from the U.S. Food and Drug Administration, the Food and Drug Administration (FDA), before he could begin experimental treatment.
The patient recalls fearing that her cancer could worsen from stage 3 to stage 4 during this waiting period. “But they assured me that cancer doesn’t grow in a day.”
Sasha Roth has been closely monitored to ensure it is safe to wait for treatment and keep her in a clinical trial. He started the experimental therapy in December 2019. After the first infusion, he went on vacation to Florida and says that he did not experience any side effects. It even kept flowing.
Halfway through the clinical trial, Roth’s tumor was visibly shrinking. Six months later, when Roth was switching to chemotherapy, he received a phone call from Cercek on Friday night, telling him to cancel his move to New York. Researchers would adjust the clinical trial; chemotherapy – along with radiation therapy or surgery – would no longer be needed, 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 seek a second opinion.
Roth is also grateful for the scientific progress given the prevalence of cancer in her family. Roth’s father died of a brain tumor in 1999, and his mother is currently battling cancer in her “last days of life.” Thanks to innovations in this field, he feels optimistic about his own future.
“I feel a universal sense of gratitude – but also hope for others,” he says. “Hope for all kinds of cancer.”
PUBLIC Exclusive / The Washington Post