Immunotherapy for Endometrial Cancer

Immunotherapy is treatment with drugs that help a person’s own immune system better recognize and kill cancer cells.

Immune checkpoint inhibitors

An important part of the immune system is its ability to keep itself from attacking the body's normal cells. 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 endometrial cancers.

PD-1 inhibitors

Pembrolizumab (Keytruda) and dostarlimab (Jemperli) are drugs that target PD-1, a protein on 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 immune response against cancer cells. This can shrink some tumors or slow their growth.

Pembrolizumab can be used by itself to treat advanced endometrial cancers, typically after other treatments have been tried, if surgery or radiation are not good options, and if the cancer cells have 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 the cells have many gene mutations

Tumor cells can be tested for these changes.

Pembrolizumab can also be used along with the targeted drug lenvatinib (Lenvima) to treat advanced endometrial cancers that are not MMR deficient (dMMR) or MSI high (MSI-H), typically after at least one other drug treatment has been tried.

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

Dostarlimab can be used to treat advanced or recurrent endometrial cancer, either:

• Along with chemo as the first treatment (and then afterward by itself), if the cancer cells have a defect in a mismatch repair gene (dMMR) or a high level of microsatellite instability (MSI-H)
• By itself, after chemo has been tried (and if surgery and radiation aren't good options), if the cancer cells have a defect in a mismatch repair gene (dMMR)

Tumor cells can be tested for these changes.

This drug is given as an intravenous (IV) infusion, typically once every 3 weeks at first, and then every 6 weeks.

Possible side effects

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 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 report any new side effects to your health care team right away. If you do have a serious side effect, treatment may need to be stopped and you may be given high doses of corticosteroids to suppress your immune system.