Biomarkers, targeted and immunotherapies for colorectal cancer
This section covers the following topics:
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
tests may be used to select treatments, and help patients avoid side effects from treatments that will not work for them. 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 Testing section for more information.
- Experts recommend testing all colorectal cancers for an abnormality known as MSI-H (“ high") also known as "" ( or ).
- cancers are common in people with a gene mutation. People with advanced or MSI-high colorectal cancer may respond well to a type of known as an immune checkpoint inhibitor.
- Experts recommend testing 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.
- (also known as HER2/neu or ERBB2) is a 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 . Tumors that test positive for may be treated with Herceptin or a related anti-HER2 drug, usually in combination with standard chemotherapy.
- Additional tests that may be used in colorectal cancer:
- A known as an NTRK fusion is rare in colorectal cancer. Advanced/metastatic colorectal cancer with an NTRK fusion may benefit from the Vitrakvi (larotrectinib).
- Additional tumor testing may help people learn if they are eligible for certain clinical trials.
Immunotherapies help the body’s immune system detect and attack cancer cells.
- Immune checkpoint inhibitors are often used to treat advanced or colorectal cancer that have MSI-H or ; usually after other treatments have been tried. The most common immune checkpoint inhibitors used for colorectal cancer are:
- Keytruda (pembrolizumab)
- Opdivo (nivolumab)
- Yervoy (ipilimumab)
Several targeted therapies are used to treat advanced or colorectal cancer. Some work best for people with or without a certain .
- 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 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 colorectal cancer that has come back after treatment with other drugs.
- Herceptin (trastuzumab) is used to treat advanced or recurrent 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
|Name of drug||Type of agent||Cancer||Indication|
|Keytruda (pembrolizumab)||Immune checkpoint inhibitor||or unresectable colorectal cancer||For first-line treatment of or unresectable colorectal cancer||High (MSI-H) or ()|
|or unresectable||For treatment of that have progressed after treatment and for which there are no other treatment options||High (MSI-H) or ()|
|or unresectable||For the treatment of that have progressed after treatment and for which there are no other treatment options||High (TMB-H)|
|or unresectable colorectal cancer||Cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan||High (MSI-H) or ()|
|Immune checkpoint inhibitor||colorectal cancer||
As a single agent or in combination with Yervoy (ipilimumab) for cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan
|High (MSI-H) or ()|
|Yervoy (ipilumumab)||Immune checkpoint inhibitor||colorectal cancer||Combined with Opdivo (nivolumab) for cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan||High (MSI-H) or ()|
|Monoclonal antibody for vascular endothelial growth factor (VEGF)||colorectal cancer||Combined with intravenous 5-fluorouracil-based chemotherapy for first- or second-line treatment||No required|
|colorectal cancer||In combination with chemotherapy for second-line treatment in patients who have progressed on a first-line Avastin-containing regimen||No required|
|Monoclonal antibody for vascular endothelial growth factor (VEGF)||colorectal cancer||Combined with FOLFIRI chemotherapy, for treatment after disease progression on, or after prior therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine||No required|
|Monoclonal antibody for epidermal growth factor receptor (EGFR)||colorectal cancer||Combined with FOLFIRI for first-line treatment, or combined with irinotecan for cancers that no longer respond to irinotecan-based chemotherapy or as a single agent in patients who have progressed after oxaliplatin- and irinotecan-based chemotherapy||EGFR positive and KRAS mutation negative|
|Monoclonal antibody for epidermal growth factor receptor (EGFR)||colorectal cancer||Combined with FOLFOX for first-line treatment||Negative for KRAS and NRAS tumor mutations|
|colorectal cancer||As a single therapy following disease progression after prior treatment with fluoropyrimidine, oxaliplatin, and irinotecan-containing chemotherapy||Negative for KRAS and NRAS tumor mutations|
The National Comprehensive Cancer Network (NCCN) provides expert-developed guidelines for tumor testing for people with colorectal cancer. NCCN recommends the following for tumor testing in people with colorectal cancer:
- All newly-diagnosed colorectal cancers should be tested for (MSI) or ( or ).
- People diagnosed with advanced MSI-H/dMMR cancers may benefit from treatment with a type of known as immune checkpoint inhibitors.
- Depending on MMR/MSI test results, referral for genetic counseling for an inherited gene mutation associated with .
- Additional tumor tests may help determine treatment options in colorectal cancer. This includes testing for:
- BRAF V600E
The following are studies enrolling people with advanced colorectal cancer.
- NCT03607890: Nivolumab and Relatlimab in Advanced MSI-H Cancers Resistant to Prior PD-(L)1 Inhibitor. The purpose of this study is to evaluate the safety, effectiveness, and tolerability of using the drugs nivolumab and relatlimab in patients with high (MSI-H) resistant to prior PD-(L)1 therapy.
- NCT02997228: Chemotherapy, Bevacizumab, and/or Atezolizumab for / MSI-H Colorectal Cancer (COMMIT Study). The study will compare how well a combination of chemotherapy and works compared with an drug alone.
- NCT03337087: Treating Pancreatic, Colorectal, Gastroesophageal, or Biliary Cancer with Chemotherapy and . This study will look at how the , works with chemotherapy in treating patients with pancreatic, colorectal, gastroesophageal, or biliary cancer.
- NCT04008030: Nivolumab, Nivolumab Plus Ipilimumab, or Chemotherapy for High (MSI-H) Colorectal Cancer.The study will compare the combination of agents nivolumab (Opdivo) plus ipilimumab (Yervoy) in patients who have MSI-H or colorectal cancer versus using nivolumab alone or chemotherapy.
A number of other clinical trials for patients with colorectal cancer can be found here.