A new approach to treating Stage II and III MSI-H/dMMR bowel cancer

When bowel cancer is detected in its earliest stages, 99% of cases can be treated successfully. In contrast, for patients with stage III or IV bowel cancer, the five-year survival rate is 71% and 13% respectively.

10-15% of patients with stage II or III bowel cancer, and 5% with stage IV bowel cancer, have microsatellite instability-high/deficient DNA mismatch repair (MSI-H/dMMR) disease.

Mismatch repair (MMR) is a normal process that occurs in our cells to correct any errors that occur during DNA replication. Defects in the MMR process can lead to tumours with high microsatellite instability (MSI-H).

A new phase II clinical trial, NEOPRISM-CRC, has found that giving the immunotherapy drug Keytruda (pembrolizumab) prior to surgery instead of chemotherapy can help improve outcomes for people with stage II or III MSI-H/dMMR bowel cancer.

Pembrolizumab stimulates the immune system, including T cells (lymphocytes) which eliminate pathogens and harmful or damaged cells (such as cancer) from the body.

In the study, 100% of patients involved in the trial had no evidence of disease (NED) following treatment. 59% of participants treated with Keytruda prior to surgery had no signs of cancer following surgery, and the remaining 41% had their tumours removed during surgery.

According to the researchers, when standard-of-care conventional chemotherapy is administered in patients with this genetic profile, less than 5% of them are NED following surgery.

“Our results indicate that pembrolizumab is a safe and highly effective treatment to improve outcomes in patients with high-risk [bowel] cancer, increasing the chances of curing the disease at an early stage,” said Kai-Keen Shiu, consultant medical oncologist and lead study researcher at the University College London Cancer Institute.

“We need to wait to see whether the patients in our trial remain cancer-free over a longer period of time, but initial indications are extremely positive,” he added.

The researchers also noted that with the new approach, patients didn’t require postoperative chemotherapy.

“Immunotherapy prior to surgery could well become a gamechanger for patients with this type of cancer. Not only is the outcome better, but it saves patients from having more conventional chemotherapy, which often has more side effects,” said Mark Saunders, consultant clinical oncologist at The Christie NHS Foundation Trust.

“In the future, immunotherapy may even replace the need for surgery,” he added.

The researchers plan to assess overall survival (OS) and relapse rates over a follow-up period of five years.