Immunotherapy for Colorectal Cancer

Immunotherapy is the use of medicines to help a person’s own immune system better recognize and destroy cancer cells.

For people with either early- or advanced-stage colorectal cancer, immunotherapy is now a cornerstone of treatment if the tumor cells test positive for certain gene changes such as dMMR (deficient mismatch repair) or MSI-H (microsatellite instability-high).

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 “checkpoint” proteins on immune cells, which act like switches 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 called immune checkpoint inhibitors target these checkpoints, which can help to restore the immune response against colorectal cancer cells.

These drugs 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 defects in one of the mismatch repair (MMR) genes (dMMR). They might be used in different situations, such as:

• As the initial treatment for locally advanced rectal cancer
• Before surgery for early-stage colon cancer
• To treat cancer that can’t be removed with surgery, has come back (recurred) after treatment, or has spread to other parts of the body (metastasized)

PD-1 and PD-L1 inhibitors

PD-1 is a checkpoint protein on immune cells called T cells. It acts as an “off switch” to help keep the T cells from attacking normal cells. PD-1 does this by attaching to PD-L1, a protein found on some cells. When PD-1 binds to PD-L1, it tells the T cell not to attack. Some cancer cells have large amounts of PD-L1, which helps them avoid being attacked by the immune system.

Drugs that target either PD-1 or PD-L1 can block this binding and boost the immune response against cancer cells.

Examples of PD-1 and PD-L1 inhibitors include:

• Nivolumab (Opdivo, Opdivo Qvantig)
• Pembrolizumab (Keytruda, Keytruda Qlex)
• Atezolizumab (Tecentriq, Tecentriq Hybreza)
• Dostarlimab (Jemperli)

These drugs might be given alone or along with chemotherapy, typically once every 2 to 6 weeks, depending on the drug and why it’s being given. 

All of these drugs can be given as an infusion into a vein (IV). Some of them can also be given as an injection under the skin instead, which takes less time.

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. 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 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.