Rectal cancer trial achieves 100 percent response rate

Four of the first patients treated in the Memorial Sloan Kettering clinical trial

for the treatment of rectal cancer. Image credit – MSK click to view video

CANCER DIGEST – June 11, 2022 – In a small clinical trial involving 12 patients with rectal cancer, all 12 experienced complete eradication of their cancer after receiving a new immunotherapy treatment, according the findings published in the June 5, 2022 New England Journal of Medicine.

In the trial, led by Drs. Andrea Cercek and Luis Diaz, Jr. at New York’s Memorial Sloan Kettering Cancer Center, 12 patients were selected for the study because of a specific genetic abnormality called mismatch repair-deficiency (MMRd). This particular mutation occurs in between 5 percent and 10 percent of all rectal cancer patients.

“An MMRd tumor develops a defect in its ability to repair certain types of mutations that occur in cells," Dr. Diaz said in a press release. He heads the MSK division of Solid Tumor Oncology and holds the Grayer Family Chair. "When those mutations accumulate in the tumor, they stimulate the immune system, which attacks the mutation-ridden cancer cells."

Nevertheless, cancer has a trick to stop the immune system from attacking the tumor. Immune system cells have safety switches, called checkpoints that prevent them from attacking normal cells. Cancer cells have the ability to flip that switch to shut down the immune cells.

The new drug used in this trial is called dostarlimab (Jemperli®), which is FDA approved for the treatment of endometrial cancer. It is specifically designed to target MMRd cancer cells to turn the checkpoint back on, allowing the immune cells to attack them.

The standard approach to treating rectal cancer is to administer chemotherapy and radiation to shrink the tumor as much as possible followed by surgery to remove any remaining cancer. The trouble with that approach is it leaves the patient with bowel and bladder dysfunction as well as incontinence, infertility and sometimes with sexual dysfunction.

Drs. Diaz and Cercek decided to try using immunotherapy first to shrink the tumor completely and then monitor closely for any recurrence. To further increase the odds of success, they chose a subset of patients whose stage 2 or 3 rectal cancers specifically had the MMRd mutation. Patients were treated with intravenous dostarlimab every three weeks for six months.

Using MRI, endoscopy and other imaging tests to monitor for recurrence they found that the tumors shrank much more rapidly than anticipated.

“My research nurse Jenna Sinopoli would tell me, ‘The patient has only received one treatment and already they’re not bleeding anymore and their terrible pain has gone away.’ ” Dr. Cercek said in a press release. “Patients came to my office after just two or three treatments and said, ‘This is incredible. I feel normal again.’ ”

In patient after patient the complete response was repeated in all 12 patients initially enrolled, and now in two more who have enrolled. So far, none of the patients have needed surgery or any additional treatment, and there has been no recurrence of the cancer in follow ups ranging from six months to more than two years.

The clinical trial is continuing and Dr. Cercek and Diaz are asking for rectal cancer patients to get tested for MMRd and if they are positive, to have their physicians contact them regardless of cancer stage at 833-647-7597.