ATOMIC Looks at Immunotherapy in Early-Stage dMMR Colon Cancer

Rachel Narozniak
Published: Monday, Oct 07, 2019
Frank Sinicrope, MD

Frank Sinicrope, MD

Investigators are seeking to determine whether immunotherapy that has been effective in metastatic colon cancers with deficient DNA mismatch repair (dMMR) can be applied to earlier-stage disease, specifically, nonmetastatic stage III colon cancer.

Among stage III colon cancers, approximately 11% are dMMR positive, according to Sinicrope, who is a gastroenterologist, internist, and oncologist at Mayo Clinic in Rochester, Minnesota.

Figure. Atezolizumab With Combination Chemotherapy in Stage III dMMR Colon Cancer (Click to Enlarge)

A Biomarker-Driven Approach

Investigators are enrolling patients whose tumors have MSI due to dMMR. In ATOMIC, dMMR status serves as the biomarker predictive of response to atezolizumab. Patients’ tumor tissue is stained for the expression of 4 proteins—MLH1, MSH2, MSH6, and PMS2—that govern MMR. The absence of 1 or more of the proteins, as detected by immunohistochemical (IHC) staining, denotes dMMR.2 In contrast, a normal IHC test implies that all 4 MMR proteins are expressed and retained.4 Approximately 15% of CRCs have dMMR, and this rate decreases by stage.2

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