MSH2 (Lynch Syndrome): Cancer Treatment

Cancer Treatment for People with Inherited MSH2 Mutations

Testing positive for an inherited MSH2 mutation may affect your treatment options or eligibility for clinical trials studying which treatments work best. To learn more about standard of care treatment options for specific types of cancer, visit our section on Cancer Treatment by Cancer Type. People with an MSH2 mutation who have been diagnosed with cancer may benefit from biomarker testing and may qualify for clinical trials looking for more effective treatments for cancer.

The following are examples of situations where an MSH2 mutation may play a part in treatment decision-making. 

Immunotherapy treatment

Most cancers in people with an inherited MSH2 mutation will have a tumor biomarker known as “MSI-high" or "MSI-H" (microsatellite instability). This biomarker indicates that the tumor has a feature known as "mismatch repair deficiency," which is also known by the abbreviations dMMR or MMR-D. Testing tumors for mismatch repair deficiency or MSI-High can be important, because these tumors are more likely to respond to immunotherapy agents known as immune checkpoint inhibitors. 

Early-stage MSI-H colorectal cancer

• In people with stage 2 colorectal cancer, MSI-H cancers have a good prognosis and may not benefit from 5-flourouracil (chemotherapy used in colorectal cancer) adjuvant therapy. 
• People with stage 2 or stage 3 rectal cancer that is MSI-H, may benefit from neoadjuvant treatment (before surgery) with Jemperli (dostarlimab).

Advanced MSI-H colorectal cancer

• Jemperli (dostarlimab) may be used to treat MSI-H or dMMR advanced colorectal cancer in people whose cancer got worse after chemotherapy.  
• Keytruda (pembrolizumab) is an immune checkpoint inhibitor used to treat metastatic or advanced colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.
• Opdivo (nivolumab) is an immune checkpoint inhibitor used alone or in combination with Yervoy (ipilimumab) for metastatic cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.

dMMR endometrial cancer

• Infimzi (durvalumab) is an immunotherapy that is approved in combination with chemotherapy to treat recurrent and advanced endometrial cancer that is mismatch repair-deficient.
• Jemperli (dostarlimab) is an immunotherapy that is approved to treat recurrent and advanced endometrial cancer that is mismatch repair-deficient.
• Keytruda (pembrolizumab) is an immunotherapy that is approved to treat MSI-H or dMMR advanced or recurrent endometrial cancer that came back or got worse after previous treatment and for which there are no other treatment options.

Immune checkpoint inhibitors for treating any type of advanced MSI-H cancer

• Keytruda (pembrolizumab) is approved for the treatment of any solid tumors that test MSI-H, have progressed after treatment and for which there are no other treatment options.

In the News