Immunotherapy for Stomach Cancer

Immune checkpoint inhibitors

An important part of the immune system is its ability to prevent 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 that target these checkpoints (called immune checkpoint inhibitors) can be used to treat some people with stomach cancer (also known as gastric cancer).

PD-1 inhibitors

Nivolumab (Opdivo), pembrolizumab (Keytruda), and tislelizumab (Tevimbra) are drugs that target PD-1, a protein on immune system cells called T cells. The PD-1 protein normally helps keep T cells from attacking other cells in the body. By blocking PD-1, these drugs boost the immune response against cancer cells. This can shrink some tumors or slow their growth.

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

This drug is given as an intravenous (IV) infusion, usually once every 2 or 3 weeks.

Pembrolizumab can be used as part of the first treatment for people with advanced stomach cancer, either:

• Along with chemotherapy if the cancer cells test negative for HER2, or
• Along with chemotherapy and the targeted drug trastuzumab, if the cancer cells test positive for both HER2 and for the PD-L1 protein

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, 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.

Possible side effects of immune checkpoint inhibitors

Side effects of these drugs can include:

• Feeling tired or weak
• Fever
• Cough
• Nausea
• Itching
• Skin rash
• Loss of appetite
• Muscle or joint pain
• Shortness of breath
• 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 this causes the immune system to attack 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.