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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 “checkpoints” – proteins on immune cells 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. Newer drugs that target these checkpoints hold a lot of promise as liver cancer treatments.

PD-1 and PD-L1 inhibitors

PD-1 is a checkpoint protein on immune cells called T cells. When PD-1 attaches to PD-L1, a protein on other cells in the body, it acts as a type of “off switch” that basically tells the T cell to leave the other cell alone. Some cancer cells have large amounts of PD-L1, which helps them hide from an immune attack. Drugs that target either PD-1 or PD-L1 can block this binding and boost the immune response against cancer cells.

Atezolizumab (Tecentriq) and durvalumab (Imfinzi) target the PD-L1 protein. Blocking this protein can help boost the immune response against cancer cells. This can shrink some tumors or slow their growth.

Atezolizumab can be used along with the targeted drug bevacizumab (Avastin) as the first treatment for liver cancer that cannot be treated by surgery or that has spread to other organs.

Durvalumab can be used with another immunotherapy drug tremelimumab (Imjudo) as the first treatment for liver cancer that cannot be removed with surgery.

These drugs are given as an infusion into a vein (IV), typically once every 2, 3, or 4 weeks. Atezolizumab (as Tecentriq Hybreza) can also be given as an injection under the skin (subcutaneously) over several minutes, typically once every 3 weeks.

Pembrolizumab (Keytruda) and nivolumab (Opdivo) are drugs that target PD-1, which can help boost the immune response against cancer cells. This can shrink some tumors or slow their growth.

These drugs can be used in people with advanced liver cancer who have previously been treated (such as with the targeted drug sorafenib [Nexavar]). Pembrolizumab can be used by itself, while nivolumab is typically used along with ipilimumab (see below).

These drugs are given as an intravenous (IV) infusion, typically every 2, 3, 4, or 6 weeks.

CTLA-4 inhibitor

Ipilimumab (Yervoy) and tremelimumab (Imjudo) are other types of drugs that boost the immune response, but they have a different target. They block CTLA-4, another protein on T cells that normally helps keep them in check.

Tremelimumab (Imjudo) can be used with another immunotherapy drug durvalumab as the first treatment for liver cancer that cannot be removed with surgery. It is given as an intravenous (IV) infusion once every 4 weeks. 

Ipilimumab can be used in combination with nivolumab to treat liver cancer that has previously been treated (such as with the targeted drug sorafenib). This drug is given as an intravenous (IV) infusion, usually once every 3 weeks for 4 treatments.

Possible side effects of 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
• Constipation or diarrhea

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, kidneys, skin, or other organs.

Serious side effects seem to occur more often with ipilimumab than with the PD-1 and PD-L1 inhibitors.

It’s very important to report any new side effects to your health care team promptly. 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.