Immunotherapy for Colorectal Cancer

Immunotherapy is the use of medicines to help a person’s own immune system better recognize and destroy cancer cells. Immunotherapy can be used to treat some people with advanced colorectal cancer.

Immune checkpoint inhibitors

An important part of the immune system is its ability to keep itself from attacking the body's normal cells. To do this, it uses “checkpoints” - proteins on immune cells that need to be turned on (or off) to start an immune response. Colorectal cancer cells sometimes use these checkpoints to avoid being attacked by the immune system. Drugs that target these checkpoints help to restore the immune response against colorectal cancer cells.

Drugs called checkpoint inhibitors can be used for people whose colorectal cancer cells have tested positive for specific gene changes, such as a high level of microsatellite instability (MSI-H), or changes in one of the mismatch repair (MMR) genes. These drugs might be used to treat people whose cancer can't be removed with surgery, has come back (recurred) after treatment, or has spread to other parts of the body (metastasized).

PD-1 inhibitors

Pembrolizumab (Keytruda) and nivolumab (Opdivo) are drugs that target PD-1, a protein on immune system cells called T cells that normally help keep these cells from attacking other cells in the body. By blocking PD-1, these drugs boost the immune response against cancer cells.

Pembrolizumab can be used as the first treatment for people with advanced or metastatic colorectal cancer. It is given as an intravenous (IV) infusion every 3 or 6 weeks.

Nivolumab can be used alone or with ipilimumab (see below) for people with metastatic colorectal cancer that has grown after treatment with chemotherapy. It is typically given by itself as an IV infusion every 2 or 4 weeks. If it is used along with ipilimumab, then it is given every 3 weeks.

CTLA-4 inhibitor

Ipilimumab (Yervoy) is another drug that boosts the immune response, but it has a different target. It blocks CTLA-4, another protein on T cells that normally helps keep them in check.

This drug can be used along with nivolumab (Opdivo) to treat colorectal cancer, but it’s not used alone. It is given as an intravenous (IV) infusion, usually once every 3 weeks for 4 treatments. 

Possible side effects of immunotherapy

Side effects of these drugs include fatigue, cough, nausea, diarrhea, skin rash, loss of appetite, constipation, joint pain, and itching.

Other, more serious side effects occur less often.

Infusion reactions: Some people might have an infusion reaction while getting these drugs. This is like an allergic reaction, and can include fever, chills, flushing of the face, rash, itchy skin, feeling dizzy, wheezing, and trouble breathing. It’s important to tell your doctor or nurse right away if you have any of these symptoms while getting these drugs.

Autoimmune reactions: These drugs work by basically removing one of the safeguards on the body’s immune system. Sometimes the immune system starts attacking other parts of the body, which can cause serious or even life-threatening problems in the lungs, intestines, liver, hormone-making glands, nerves, skin, kidney, or other organs.

It’s very important to report any new side effects during or after treatment with any of these drugs to your health care team promptly. If serious side effects do occur, you may need to stop treatment and take high doses of corticosteroids to suppress your immune system.