Immunotherapy for Oral Cavity and Oropharyngeal Cancer

Immunotherapy uses medicines to help your immune system better recognize and destroy cancer cells. Many types of immunotherapy are being tested in clinical trials, and some are used to treat oral cavity and oropharyngeal cancer.

Immune checkpoint inhibitors

An important part of your immune system is its ability to keep itself from attacking normal cells in your body. To do this, it uses “checkpoint” proteins on immune cells. These proteins 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 checkpoint inhibitors, can be used to treat some people with oral cavity or oropharyngeal cancer.

PD-1 inhibitors

The type of checkpoint inhibitor used to treat oral cavity and oropharyngeal cancers is called a PD-1 inhibitor. These drugs target or block PD-1, which is a checkpoint protein on certain immune system cells called T cells.

PD-1 normally helps keep T cells from attacking other cells in the body, including some cancer cells. By blocking PD-1, these drugs boost the body’s immune response against cancer cells. This can shrink some tumors or slow their growth.

The PD-1 inhibitors used to treat these cancers include:

• Pembrolizumab (Keytruda)
• Nivolumab (Opdivo)

A PD-1 inhibitor may also be given alone if the disease has worsened on chemo or if the tumor:

• Has a high tumor mutational burden (TMB-H), meaning the cells have many gene mutations
• Is PD-L1 positive, meaning the cancer cells have a high amount of the PD-L1 protein on their surface
• Has a high level of microsatellite instability (MSI-H), meaning there are a lot of gene changes in a short, repeated sequence of DNA or a defect in a mismatch repair gene (dMMR)

How are these drugs given?

Pembrolizumab may be given alone or with radiation, chemotherapy, or targeted therapy (cetuximab). Nivolumab may be given alone.

These drugs are typically given once every 2 to 6 weeks, depending on the drug and why it’s being given. Both pembrolizumab and nivolumab can be given as an infusion into a vein (IV). Nivolumab can also be given as an injection under the skin over several minutes.

Possible side effects

Common side effects of PD-1 inhibitors can include:

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

More serious side effects that occur less often include:

• Infusion reactions. This is like an allergic reaction. It can happen while getting one of these drugs and can include fever, chills, flushing of the face, rash, itchy skin, dizziness, wheezing, and trouble breathing. Tell your treatment team right away if you have any of these symptoms during your infusion.
• Autoimmune reactions. These drugs remove 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.

It’s very important to tell your health care team right away if you have any new side effects during or after treatment with any of these drugs. If you have any serious side effects, you might need to stop treatment and take high doses of steroids to suppress your immune system.