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Colorectal cancer immunotherapy

This page was reviewed under our medical and editorial policy by

Maurie Markman, MD, President, Medicine & Science at CTCA.

This page was reviewed on June 9, 2022.

Immunotherapy is one type of treatment used for colorectal cancer. It uses very specific drugs to help the immune system destroy cancer cells. In particular, immunotherapy drugs called checkpoint inhibitors may be appropriate when colorectal cancer cells exhibit certain gene changes and characteristics.

One of these characteristics is the microsatellite stability status, which can be determined when cells taken during a biopsy, or tissue samples, are analyzed. Biopsy results may show:

  • Microsatellite instability-high (MSI-H), which is determined when cancer cells look highly unstable under a microscope after mismatch repair (MMR) genes stop fixing errors in the division of cells
  • Microsatellite instability-low (MSI-L)
  • Microsatellite stable (MSS)

Candidates for immunotherapy for colorectal cancer may have tumors that are MSI-H. According to a study published in the journal Familial Cancer, an estimated 15 percent of colorectal tumors are MSI-H, and most are associated with Lynch syndrome (a genetic condition that increases the risk of developing cancers, such as colon cancer). Non-MSI tumors are less likely to respond to immunotherapy.

Specific gene mutations may also affect how well treatment works. For instance, according to researchers in Gastroenterology Report, the KRAS mutation, occurring in more than 40 percent of metastatic colorectal cancer cases, hasn’t responded as well to colorectal cancer immunotherapies—until now. KRAS lung cancer research and new colon cancer trials have found promising indications that certain KRAS mutations may be amenable to newer immunotherapy treatments in colorectal cancer.

Immune checkpoint inhibitors for colorectal cancer

The MSI colorectal cancer immunotherapy drugs called immune checkpoint inhibitors take their name from one of the immune system’s key functions. Under normal circumstances, the immune system is able to activate certain proteins, referred to as checkpoints, to provoke an immune response and stop invaders from attacking healthy cells in the body. Colorectal cancer cells sometimes avoid attacks from the immune system by taking advantage of these checkpoints. Checkpoint inhibitors may help restore the normal functioning of the immune system so it can recognize and attack cancer cells.

Checkpoint inhibitors may be appropriate for:

  • Colorectal cancer that’s recurred after prior treatment
  • A cancerous tumor too large to remove with surgery
  • Colorectal cancer that’s spread to other parts of the body

Types of checkpoint inhibitors

PD-1 inhibitors

PD-1 is a type of protein on the immune system’s T-cells. PD-1 block T-cells from attacking other cells. PD-1 inhibitors are designed to improve the way the immune system responds to cancer.

PD-1 inhibitors for colorectal cancer include:

Opdivo® (nivolumab) may be used for colorectal cancer that spread after the patient received initial treatment with certain chemotherapy drugs. It’s usually given as an intravenous (IV) infusion every two or four weeks. It may also be combined with Yervoy® (ipilimumab) for MSI-H or dMMR (deficient mismatch repair) metastatic colorectal cancer.

Keytruda® (pembrolizumab) may be used for advanced colorectal cancer or for colorectal cancer that’s already spread. It’s usually given as an IV infusion every three or six weeks.

Jemperli® (dostarlimab) may be used as treatment for recurrent or metastatic colorectal cancers that have dMMR. It’s usually given as an IV infusion every three or six weeks.

CTLA-4 inhibitors

CTLA-4 is another type of protein on T cells. CTLA-4 inhibitors may also be used to help improve the immune system’s response. Yervoy, which is given as an infusion with nivolumab, is a CTLA-4 inhibitor.

Side effects of immunotherapy for colorectal cancer

As with other types of cancer treatment, side effects are commonly associated with immunotherapy. These may occur when the drug attacks healthy cells in the body along with cancer cells. Side effects include:

  • Digestive changes such as diarrhea
  • Fatigue
  • Nausea
  • Loss of appetite
  • Itching
  • Joint pain
  • Coughing
  • Reactions to the infusion, including fever, chills, dizziness and trouble breathing
  • Skin rashes

There’s also the risk of an autoimmune reaction, which occurs when the body mistakenly attacks itself. This may happen because of the specific way immunotherapy works. Your care team will frequently monitor you for autoimmune reactions, but let them know if you have any unusual or concerning symptoms.

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