New study expands immunotherapy eligibility for colorectal and endometrial cancer patients

A new study shows thousands more patients diagnosed with colorectal and endometrial cancers could benefit from immunotherapy than are currently offered it. Researchers showed the importance of looking at DNA Mismatch Repair Deficiency (MMR-D) as a guiding marker for treatment decisions using immune checkpoint inhibitors (ICIs). MMR-D is associated with an increased risk of developing several types of cancer and is the most common cause of hereditary endometrial cancer.

The study, which published in Cancer Cell on December 28, compared two lab testing methods to diagnose cancers-; traditional immunohistochemistry (IHC) (a lab technique that uses antibodies to detect antigens in tissues) -; and next-generation sequencing (NGS) -; a new technology used for DNA sequencing that can detect specific patterns of mutations. The researchers discovered that NGS offers a more accurate assessment of MMR status.

We found that 1% of patients with colorectal cancer and 6% of patients with endometrial cancer are functionally mismatch repair-deficient but are still missed by IHC, the current standard of care testing. However, these cancers are detected by NGS. Importantly, we showed that these patients (missed by IHC and detected by NGS) achieved long-term benefit from immunotherapy. We recommend revisiting guidelines for mismatch repair testing to include both this NGS and IHC."

Amin Nassar, MD, senior author of the study and member of Yale Cancer Center

Researchers estimate that implementing NGS alongside IHC could identify an additional 6,000 patients in the United States annually who could benefit from life-extending immunotherapy. These patients would not be offered immunotherapy if IHC was used alone.

The researchers call for larger studies to further validate these findings in patients with colorectal and endometrial cancers and explore the application of NGS in other cancer types.

Nassar is a clinical fellow at Yale Cancer Center who did much of the work while he was a resident at Brigham and Women's Hospital. He was joined by first author Elias Bou Farhat, MD, of Brigham and Women's Hospital.

Source:
Journal reference:

Bou Farhat, E., et al. (2023). Benchmarking mismatch repair testing for patients with cancer receiving immunotherapy. Cancer Cell. doi.org/10.1016/j.ccell.2023.12.001.

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