Cancer test indicate promise for expanding immunotherapy to more patients

Immunotherapy is a highly effective treatment for people whose malignancies have mismatch repair weakness, and a new study finds more cancer patients who may benefit from it. Researchers from Brigham and Women’s Hospital, a founding member of the Mass General Brigham health care system, discovered that immunohistochemistry, the current standard of care test for this condition, missed nearly 6% of endometrial cancer patients and 1% of colorectal cancer patients with mismatch repair deficiency. In these missing cases, the ailment was found using next-generation sequencing, which experts believe could find 6,000 additional patients in the United States who would not have received immunotherapy otherwise. The findings were reported in the journal Cancer Cell.

“In colorectal cancer and endometrial cancer, which are the two types of cancer where mismatch repair deficiency is most commonly seen, immunotherapy is not the standard treatment unless a patient has this condition,” said first author Elias Bou Farhat, MD, a postdoctoral research fellow in Brigham and Women’s Hospital’s division of Pulmonary and Clinical Care Medicine. “However, patients with this condition, even those with late-stage cancer, who receive immunotherapy can live for years and, in some cases, be cured.” Incorporating next-generation sequencing as a complementary testing strategy could benefit cancer patients at all stages, from pre-treatment to advanced.”

Each year, more than 150,000 persons in the United States are diagnosed with colorectal cancer, and more than 65,000 are diagnosed with endometrial cancer. Patients with these two forms of cancer frequently have high rates of mismatch repair deficiency, a hereditary condition in which errors in DNA develop due to a lack of specific repair proteins. This condition inhibits DNA’s capacity to repair itself and can result in a variety of cancers. Previous study has indicated that cancer patients with this disease usually respond well to immunotherapy treatment, which harnesses the patient’s own immune system to attack cancer.

The researchers examined a group of 1,655 patients from Brigham and Women’s Hospital and Dana-Farber Cancer Institute who had colorectal or endometrial cancer and got both immunohistochemistry and next-generation sequencing testing. The researchers discovered that approximately 6%

Immunohistochemistry missed 1% of endometrial cancer patients and 1% of colorectal cancer patients who were mismatch repair weak, but next-generation sequencing detected them. These patients responded better to immunotherapy than conventional treatments, and their survival and treatment results were comparable to those who failed both tests.

Next-generation sequencing is a more sensitive test since it searches for more mutant features than immunohistochemistry. While current research implies that next-generation sequencing will be a more sensitive diagnostic tool in these circumstances, more research is needed to confirm and generalize the findings of this study.

The data from the trial also revealed that in individuals with the same cancer kind and stage, those who did not receive immunotherapy fared worse than those who did.

“We don’t want to miss these patients or risk depriving them of a treatment that could have long-term benefits,” said senior author Amin Nassar, MD, a Yale Cancer Center member who completed much of the work as a resident at Brigham and Women’s Hospital. “We also want to avoid giving patients treatments that could be more toxic and/or less effective—we want to treat patients with the appropriate therapy.”

For more information: Benchmarking mismatch repair testing for patients with cancer receiving immunotherapy, Cancer Cell, https://doi.org/10.1016/j.ccell.2023.12.001