Biomarkers, targeted and immunotherapies for colorectal cancer

This section covers the following topics:

• Tumor biomarker testing for treatment selection 
• Immunotherapy
• Targeted therapy

Biomarker tests

Biomarker tests look at samples of blood, tumor or other tissue for changes or abnormalities caused by cancer. These tests can give doctors clues about the cancer, including:

• how fast the cancer is growing
• which treatments are most likely to work
• whether or not the cancer is responding to treatment or growing
• whether or not the cancer has come back after remission

Biomarkers for treatment selection

Biomarker tests may be used to select treatments, and help patients avoid side effects from treatments that will not work for them. Biomarker tests used to select a specific treatment are sometimes called "companion diagnostic tests." These tests may be done on tumor tissue or (in many cases) on blood. See our Biomarker Testing section for more information. 

• Experts recommend testing all colorectal cancers for an abnormality known as MSI-H (“microsatellite instability high") also known as "mismatch repair deficiency" (dMMR or MMR-D).
  • MSI-high cancers are common in people with a Lynch syndrome gene mutation. People with advanced or metastatic MSI-high colorectal cancer may respond well to a type of immunotherapy known as an immune checkpoint inhibitor. 
• Experts recommend testing metastatic colorectal cancers for the following biomarkers:
  • A specific mutation in a gene known as BRAF.  Tumors with the mutation called V600E, may respond to targeted therapies known as BRAF inhibitors. 
  • HER2 (also known as HER2/neu or ERBB2) is a biomarker commonly used in breast cancer to select patients who would benefit from anti-HER2 therapy (for example Herceptin (trastuzumab). In advanced colorectal cancer, tumors that test negative for RAS and BRAF mutations may be tested for HER2. Tumors that test positive for HER2 may be treated with Herceptin or a related anti-HER2 drug, usually in combination with standard chemotherapy.
• Additional biomarker tests that may be used in colorectal cancer:
  • A biomarker known as an NTRK fusion is rare in colorectal cancer. Advanced/metastatic colorectal cancer with an NTRK fusion may benefit from the targeted therapy Vitrakvi (larotrectinib).
  • Additional tumor biomarker testing may help people learn if they are eligible for certain clinical trials. 

Immunotherapies 

Immunotherapies help the body’s immune system detect and attack cancer cells.

• Immune checkpoint inhibitors are often used to treat advanced or metastatic colorectal cancer that have MSI-H or dMMR; usually after other treatments have been tried. The most common immune checkpoint inhibitors used for colorectal cancer are:
  • Keytruda (pembrolizumab)
  • Opdivo (nivolumab)
  • Yervoy (ipilimumab)

Targeted therapies

Several targeted therapies are used to treat advanced or metastatic colorectal cancer.  Some work best for people with or without a certain biomarker. 

• Anti VEGF therapies block tumors from forming blood vessels. Anti VEGF drugs used to treat colorectal cancer include:
  • Avastin (bevacizumab) 
  • Cyramza (ramucirumab)
  • Zaltrap (ziv-aflibercept)
• Anti EGFR therapies slow down tumor cell growth. Anti EGFR drugs used to treat colorectal cancer include:
  • Erbitux (cetuximab)
  • Vectibix (panitumumab)
• BRAF inhibitors are oral medications that help slow down tumor growth in advanced colorectal cancers that test positive for the tumor biomarker called a BRAF V600E mutation. BRAF inhibitors are usually given in combination with other oral targeted drugs called MEK inhibitors (e.g., trametinib [Mekinist] or binimetinib [Mektovi]). BRAF inhibitors include:
  • Tafinlar (dabrafenib)
  • Braftovi (encorafenib)
• Stivarga (regorafenib) blocks several different types of proteins in the body that tumors use to grow. Stivarga may be used to treat metastatic colorectal cancer that has come back after treatment with other drugs. 
• Herceptin (trastuzumab) is used to treat advanced or recurrent HER2-positive colorectal cancers that do not have a BRAF, KRAS or NRAS mutation.
• Vitrakvi (larotrectinib) is approved for treatment of advanced cancers that have worsened with other treatments. It targets a genetic change called an NTRK fusion. This type of genetic change is found in a range of cancers, including some colon cancers.

Table of targeted and immunotherapies for colorectal cancer