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Immunotherapy is the use of medicines to help a person's own immune system find and destroy cancer cells more effectively. It can be used to treat some people with stomach cancer (gastric cancer).

Immune checkpoint inhibitors

An important part of the immune system is its ability to keep itself from attacking normal cells in the body. 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. 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 restore the immune response against stomach cancer cells. These drugs can be used to treat some people with stomach cancer, either alone or with other treatments such as chemotherapy.

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:

• Durvalumab (Imfinzi)
• Nivolumab (Opdivo, Opdivo Qvantig)
• Pembrolizumab (Keytruda, Keytruda Qlex)
• Tislelizumab (Tevimbra)
• Dostarlimab (Jemperli)

These drugs can be used in different ways to treat stomach cancer.

Durvalumab can be used as part of the treatment for people with stomach cancer that can be removed with surgery. It is typically given with chemotherapy both before and after surgery, which is known as perioperative therapy. It is then given by itself for several more cycles of treatment.

This drug is given as an intravenous (IV) infusion, usually once every 4 weeks.

Nivolumab can be used in people with advanced stomach cancer, typically with chemotherapy.

This drug can be given as an intravenous (IV) infusion or as an injection under the skin, usually every 2 or 3 weeks.

Pembrolizumab can be used as part of the first treatment for people with advanced stomach cancer if the cancer cells test positive for the PD-L1 protein, either:

• With chemotherapy if the cancer cells test negative for HER2, or
• With chemotherapy and the targeted drug trastuzumab, if the cancer cells test positive for HER2

This drug can also be used after other treatments including chemotherapy have been tried, and if the cancer cells test positive for any of the following:

• A high level of microsatellite instability (MSI-H) or a defect in a mismatch repair gene (dMMR)
• A high tumor mutational burden (TMB-H), meaning they have many gene mutations

This drug is given as an intravenous (IV) infusion or as an injection under the skin, typically once every 3 or 6 weeks.

Tislelizumab can be used along with chemotherapy as a first treatment in people with advanced stomach cancer, if the cancer cells test negative for the HER2 protein and positive for the PD-L1 protein.

This drug is given as an intravenous (IV) infusion, usually once every 3 weeks.

Dostarlimab can be used for advanced or recurrent cancers if the cancer cells test positive for a high level of microsatellite instability (MSI-H) or a defect in a mismatch repair gene (dMMR).

This drug is given as an intravenous (IV) infusion, usually once every 3 or 6 weeks.

Possible side effects of immune checkpoint inhibitors

Common side effects of these drugs can include:

• Feeling tired or weak
• Fever
• Cough
• Nausea
• Itching
• Skin rash
• Loss of appetite
• Muscle or joint pain
• Constipation or diarrhea

Other, more serious side effects occur less often. These can include:

Infusion reactions: Some people might have an infusion reaction while getting one of 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 one of 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 lead to serious or even life-threatening problems in the lungs, intestines, liver, hormone-making glands, kidneys, skin, or other organs.

It’s very important to report any new side effects to your health care team right away. If serious side effects do occur, treatment may need to be stopped, and you may get high doses of corticosteroids to suppress your immune system.