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

“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 a 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 percent 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 said 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,…