Immunotherapy combination shows longer progression-free survival than chemotherapy alone for patients with a rare type of metastatic colorectal cancer

Abstract

“We’ve had very few innovations in colorectal cancer up until the immunotherapy era starting around 2014, so this is huge in this rare subtype.”

—Benjamin L. Schlechter, MD

Results from a new study published in the November 27, 2024, issue of The New England Journal of Medicine (NEJM; doi:10.1056/NEJMoa2402141) showed that a combination of two immunotherapy drugs led to longer progression-free survival (PFS) than chemotherapy alone in patients with a rare type of metastatic colorectal cancer (CRC) called mismatch repair–deficient (dMMR) adenocarcinoma. Experts consider these results practice changing.

“We’ve had very few innovations in colorectal cancer up until the immunotherapy era starting around 2014, so this is huge in this rare subtype,” says Benjamin L. Schlechter, MD, a Dana Farber Cancer Institute oncologist who specializes in gastrointestinal cancers and was not involved with the study. “It really hammers home the point that for the vast majority of these patients, first-line immunotherapy is superior to first-line chemotherapy.”

The phase 3, multinational, open-label randomized trial is known as CheckMate 8HW. It was conducted at 128 hospitals and cancer centers across 23 countries. Researchers compared the effectiveness of the immunotherapy drugs nivolumab and ipilimumab to that of chemotherapy in patients with microsatellite instability–high (MSI-H) or dMMR metastatic CRC.

MSI-H and dMMR refer to the same rare type of CRC. This subtype represents between 4% and 7% of CRCs. Unlike other CRCs, the MSI-H and dMMR subtypes have deficiencies in their DNA repair proteins that make them more susceptible to treatment with immunotherapy.

“These cancers don’t normally repair their DNA, and that happens in a few different ways,” Dr Schlechter says. “You can be born with a mutation in DNA repair that’s called Lynch syndrome, and that’s a significant proportion of these patients. Or, the cancer, through other mechanisms, can damage those same DNA repair genes. These cancers are very genetically distinct from normal tissue, which is not the case with the average colorectal cancer.”

The study authors note that patients with MSI-H or dMMR metastatic CRC have poor outcomes with standard chemotherapy with or without targeted therapy. In previous nonrandomized studies, nivolumab plus ipilimumab showed a benefit in treating the disease.

CRC survivor and patient advocate Allison Rosen, who did not have this type of cancer, is enthusiastic about the results. “The more options that rare colorectal cancers have, the better,” she says. “The treatment options haven’t changed for a long period of time, so anytime I see new research that gives any mutation a new line of therapy, it’s exciting.”