How does immunotherapy treat colorectal cancer?
When your immune system is functioning correctly, it protects your body from infection, viruses, and other pathogens and diseases. However, sometimes the immune system does not work the way it should, and it attacks normal, healthy cells. To prevent this, the immune system uses checkpoints which are proteins on immune and cancer cells that need to be turned “on or off” to induce an immune response.
Checkpoint inhibitor drugs
Colorectal cancer cells may use checkpoints to avoid being attacked by the immune system. Immunotherapy drugs target these checkpoints to restore the immune response against colorectal cancer cells.
Colorectal cancer that has tested positive for a high level of microsatellite instability (MSI-H), or changes in one of the mismatch repair (MMR) genes may be treated with checkpoint inhibitor drugs. Also, treatment of MSS (microsatellite stable) tumors is being evaluated in several clinical trials to increase patient eligibility for checkpoint inhibitor drugs.
Checkpoint inhibitor drugs may be given to patients before surgery (neoadjuvant therapy) for early-stage colorectal cancer.
Checkpoint inhibitor drugs may also be given to patients if their colorectal cancer:
- can’t be removed with surgery
- has come back (recurred) after treatment
- has spread to other parts of the body (metastasized)
Types of immunotherapy drugs
The FDA has approved several checkpoint inhibitor drugs for colorectal cancer treatment for tumors with high microsatellite instability (MSI-H) or DNA mismatch repair deficiency (dMMR). There are also several antibody-based therapies that the FDA has approved for MSI-H/dMMR and MSS/pMMR CRC diagnoses.
Checkpoint inhibitor drugs:
- Dostarlimab (Jemperli): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced colorectal cancer that has DNA mismatch repair deficiency (dMMR)
- Ipilimumab (Yervoy): a checkpoint inhibitor that targets the CTLA-4 pathway; approved in combination with nivolumab for subsets of patients with advanced colorectal cancer that has high microsatellite instability (MSI-H)
- Nivolumab (Opdivo): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced colorectal cancer that has high microsatellite instability (MSI-H), including in combination with ipilimumab
- Pembrolizumab (Keytruda): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced colorectal cancer that has high microsatellite instability (MSI-H), DNA mismatch repair deficiency (dMMR), or high tumor mutational burden (TMB-H), including as a first-line treatment.
Monoclonal Antibody drugs:
- Bevacizumab (Avastin): a monoclonal antibody that targets the VEGF/VEGFR pathway and inhibits tumor blood vessel growth; approved for subsets of patients with advanced colorectal cancer, including as a first-line therapy
- Cetuximab (Erbitux): a monoclonal antibody that targets the EGFR pathway; approved for subsets of patients with advanced, EGFR-positive colorectal cancer, including as a first-line therapy
- Panitumumab (Vectibix): a monoclonal antibody that targets the EGFR pathway; approved for subsets of patients with advanced, EGFR-positive colorectal cancer
Ramucirumab (Cyramza): a monoclonal antibody that targets the VEGF/VEGFR2 pathway and inhibits tumor blood vessel growth; approved for subsets of patients with advanced colorectal cancer, including as a first-line therapy
Common side effects from immunotherapy include:
- pain at the injection site
- rash
- swelling
- redness
- itchiness
- skin changes
You may also experience flu-like symptoms including:
- fever
- chills
- dizziness
- weakness
- fatigue
- headache
- body aches
- diarrhea
- fluid retention
- heart palpitations
- sinus congestion
- shortness of breath
Side effects from specific types of immunotherapies
Each type of immunotherapy has its own set of potential side effects. Click on the types below to learn about side effects associated with each: