Cercek dostarlimab MMR-deficient rectal cancer: What the Colorectal cancer Trial Found

A twelve-person study that changed a routine

In 2022 a team at Memorial Sloan Kettering Cancer Center published a small trial in the New England Journal of Medicine. Andrea Cercek was the first author. Twelve people with rectal cancer took one drug for six months. In all twelve, doctors could no longer find the tumor. None of them went on to radiation or surgery.

The trial is registered as NCT04165772 and is still open. Twelve people is a very small group. The idea behind the trial was not small at all.

The repair crew inside a cell

Each time a cell divides, it copies its DNA. Copying makes typos. A set of proteins hunts down those typos and fixes them. Doctors call that system mismatch repair.

In some tumors the system is broken. A pathologist may call such a tumor mismatch repair deficient, shortened to dMMR. A lab may instead report microsatellite instability high, or MSI-H. Both phrases point to the same broken proofreading.

Broken proofreading does two things. The tumor piles up a very large number of mutations. And the odd proteins built from those mutations are easy for the immune system to spot.

The National Cancer Institute puts the share of rectal adenocarcinomas with this defect at 5% to 10%. NCI also notes that these tumors tend to respond poorly to chemotherapy, whether it is given before surgery, after surgery, or for advanced disease. So this small group had both a problem and an opening.

What the usual treatment asks of a person

Rectal cancer that has grown into the wall of the rectum or reached nearby lymph nodes is called stage II or stage III. Standard care has three parts: chemotherapy, radiation to the pelvis, then surgery to remove the rectum.

That surgery works. It also carries a cost. It can change bowel habits for good, and it can affect bladder and sexual function. Some people end up with a colostomy, an opening on the belly that collects stool into a pouch. Our guide to colorectal cancer walks through those trade-offs in more detail.

What the trial did

The study was phase 2 and single-arm. Single-arm means everyone got the same treatment and there was no comparison group. Our page on clinical trial phases explains what phase 2 is meant to answer.

Each person got dostarlimab by vein every three weeks for six months. Dostarlimab is a checkpoint inhibitor, a kind of immunotherapy that blocks a protein called PD-1 so that T cells stay switched on.

The written plan was for chemotherapy, radiation, and surgery to follow. There was one exception. Anyone whose cancer had vanished on every test could skip both.

What the trial found

All 12 people had a clinical complete response. No tumor showed up on MRI, on a PET scan, on endoscopy, on a digital rectal exam, or on biopsy.

The paper reports that as 100%, with a 95% confidence interval of 74 to 100. A confidence interval is a range of values that fits the data. With only 12 people, the range stays wide, so the true rate in a larger group could be well below 100%.

At the time of the report, nobody had needed chemoradiation or surgery. Follow-up ranged from 6 to 25 months, and no cancer had come back or grown. No side effects of grade 3 or higher were reported. Grade 3 means severe.

Why your pathology report now names this test

The trial is a large part of why mismatch repair testing is standard in rectal cancer today. The test is run on tissue from the biopsy. It costs nothing extra in time for the patient, and it can point to a very different plan.

That is the wider lesson. Two tumors that look identical under a microscope can behave in opposite ways once you read their molecular profile. Biomarker testing is how that difference gets found.

When to get checked

Rectal cancer often gives warning signs, and they are easy to explain away. NCI lists bleeding from the rectum, a lasting change in bowel habits, belly pain, blocked bowels, loss of appetite, weight loss you did not plan, and unusual weakness. Blood tests may show low iron.

Bring any of these to a clinician if they last more than a couple of weeks. Do not wait for them to become dramatic.

On routine screening, the U.S. Preventive Services Task Force advises screening for everyone aged 45 to 75. For ages 76 to 85 it advises a case-by-case decision. Family history, Lynch syndrome, or long-standing colitis can move that start date earlier, so say so when you book.

What this trial cannot tell you

• Twelve people is a very small sample. There was no comparison group, and the confidence interval runs from 74% to 100%.
• Follow-up ran 6 to 25 months in this report. Rectal cancer can return years later, so durability was still an open question.
• It applies only to mismatch repair deficient tumors, which are 5% to 10% of rectal adenocarcinomas. Most people with rectal cancer are not eligible.
• The trial's own main measure was a clinical complete response lasting 12 months. At the time of this paper, not every patient had reached that mark.
• People in trials are chosen against strict rules, so results may not carry over to everyone with the same diagnosis.

For scale: SEER records five-year relative survival across all colorectal cancers at 65.4% for 2016 to 2022. That figure describes a large group over past years of treatment. It is not a forecast for any one person.

Sources

• PD-1 Blockade in Mismatch Repair-Deficient, Locally Advanced Rectal Cancer (Cercek et al., NEJM 2022)
• NCI PDQ: Rectal Cancer Treatment (Health Professional Version)
• ClinicalTrials.gov record for NCT04165772
• SEER Cancer Stat Facts: Colorectal Cancer
• USPSTF: Colorectal Cancer Screening

How this page was made

An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.

Cancer Explained is published by the National Cancer Information Foundation. It is not medical advice and does not suggest a test or treatment.

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