Identifying specific DNA or gene features—generally called “biomarkers”—in a patient with cancer allows doctors to use that information to select the best available treatment for that individual patient. Increasing understanding of genetic or genomic features that have been identified in different types of cancer has recently focused attention on tumor biomarkers found in different types of cancer, called “mismatch repair deficient” (or dMMR) and “microsatellite instability-high” (or MSI-H).
Tumors that contain the dMMR or MSI-H biomarker have abnormalities that interrupt the normal repair mechanism of the DNA inside our cells. In normal cells, the DNA or genes help to repair any abnormal activity in the cell to preserve the health of cells in our body. But in cancer that has the dMMR biomarker, the genes that would normally repair such errors are missing and, therefore, cannot repair the abnormal cells, which can lead to cancer development or growth.
Similarly, a tumor with MSI-H is missing some normal DNA features and, as a result, that person’s cells have high levels of microsatellites, an error that cannot be repaired by normal DNA activity, again leading to cancer.1 The dMMR and MSI-H biomarkers are most often found in colorectal cancer or in other gastrointestinal cancers, as well as in those with endometrial cancer. About 5% of patients with metastatic (spreading to other organs) colorectal cancer have the dMMR or MSI-H biomarker.1
Read Wenora Y. Johnson’s biomarker story of her personal experience with colorectal cancer and MSI-H.In addition to gastrointestinal cancers, dMMR and MSI-H can be found in other cancers, such as breast, prostate, and bladder, although much less often.1
Drugs for dMMR or MSI-H Biomarker
The understanding of the role of dMMR or MSI-H biomarkers in cancer has led to the first approval of a cancer drug based on a biomarker instead of a specific tumor type. In May 2017, the FDA approved Keytruda (pembrolizumab) for the treatment of any patient with advanced or metastatic solid cancer that has the dMMR or MSI-H biomarker.
“Until now, the FDA has approved cancer treatments based on where in the body the cancer started—for example, lung or breast cancers. We have now approved a drug based on a tumor’s biomarker without regard to the tumor’s original location,”2 said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence, in response to this approval.
Keytruda is an immunotherapy that was originally approved for several types of cancer, including metastatic melanoma, lung cancer, head and neck cancer, classical Hodgkin lymphoma, and urothelial (bladder) cancer. The approval in May 2017 meant that any patient with an advanced or metastatic solid tumor and the dMMR or MSI-H biomarker may be eligible to receive treatment with Keytruda.
About 2 months later, in July 2017, the FDA approved a second immunotherapy, Opdivo (nivolumab), for the treatment of patients with advanced or metastatic colorectal cancer that includes the dMMR or MSI-H biomarker.3
Both drugs are approved for use in patients whose tumor progressed after treatment with chemotherapy or other approved treatments.
References
1. Markowitz SD, Bertagnolli MM. Molecular origins of cancer: molecular basis of colorectal cancer. The New England Journal of Medicine. 2009;361(25):2449-2460.
2. US Food and Drug Administration. FDA approves first cancer treatment for any solid tumor with a specific genetic feature. May 23, 2017. www.fda.gov/newsevents/newsroom/pressannouncements/ucm560167.htm.
3. US Food and Drug Administration. FDA grants nivolumab accelerated approval for MSI-H or dMMR colorectal cancer. July 31, 2017. www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm569366.htm..
