Every Patient Who Has a GI Cancer Should Be Tested for MSI-High Status

WITH IMMUNOTHERAPY CONTINUING TO command headlines in the world of oncology, it’s no surprise that patients with a variety of cancers wonder whether the strategy might help them address and overcome their illnesses.

For those with gastrointestinal (GI) cancers, the possibilities are multiplying, as we explain in this special issue of CURE®. Well-reasoned, well-conducted clinical trials have proven that immunotherapies known as checkpoint inhibitors can treat a subset of some GI and other cancers that are considered microsatellite instability-high (MSI-high), or mismatch repair-deficient, meaning cancer cells are unable to repair their own DNA if it’s damaged. As the cells multiply, this glitch leads the cancer cells to develop a host of additional mutations, perhaps making the tumors more recognizable by the immune system — which, therefore, is a predictor that checkpoint inhibitors could be successful.

Based on these studies, the Food and Drug Administration (FDA) approved two immunotherapies for the treatment of some GI cancers that are MSI-high. Keytruda (pembrolizumab) was approved in May 2017 to treat any MSI-high advanced cancer, including some colorectal and gastric cancers. A few months later, the FDA approved Opdivo (nivolumab) to treat metastatic MSI-high colorectal cancer that has progressed despite chemotherapy.

Now, new information suggests that pairing two types of checkpoint inhibitors can further improve their effectiveness in these patients.

All this is exciting, but, unfortunately, these drugs can’t help every patient with a GI cancer — at least, not yet. About 1 in 7 colorectal cancers is MSIhigh, and 1 in 2 1/2 gastric tumors has this status. Patients in these groups should consider treatment with immunotherapies, and it’s essential that they undergo genetic testing to determine whether they are eligible.

In fact, to make sure no patient is missed, doctors should test everyone diagnosed with a GI cancer that is MSI-high — and patients should ask for the assay if it isn’t offered. For some, this might lead to the most effective possible treatment. For a rare few, it could uncover Lynch syndrome, a genetic condition associated with the development of some MSI-high GI cancers. In addition to benefiting from immunotherapy, these patients also will gain the opportunity to encourage their relatives to get tested for the inherited condition, so they can take preventive measures or have any cancers diagnosed at an early stage. Immunotherapy is an emerging set of strategies offering untold future promise. It’s extremely encouraging to watch it take hold in the treatment of GI cancers, and we look forward to progress that may, eventually, make it available to a larger swath of patients within this community.