Immunotherapy for Endometrial Cancer

An important part of your 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.

Immunotherapy is treatment with drugs that help a person’s immune system better recognize and kill cancer cells. Immunotherapy drugs used to treat endometrial cancer are immune checkpoint inhibitors.

Using PD-1 inhibitors to treat endometrial cancer

Pembrolizumab (Keytruda), dostarlimab (Jemperli), and nivolumab (Opdivo) are drugs that target PD-1, a protein on 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 or dostarlimab can be given along with chemotherapy as an initial treatment option for advanced or recurrent endometrial cancer.  The chemo given with the PD-1 inhibitor is usually carboplatin and paclitaxel.

Pembrolizumab or dostarlimab or nivolumab can be given alone after other drug treatments have been tried and if the cancer cells have been tested and found to have a high level of microsatellite instability (MSI-H) or a defect in a mismatch repair gene (dMMR). Pembrolizumab can also be given alone after other drug treatments have been tried if the cancer cells have a high tumor mutational burden (TMB-H), meaning the cells have many gene mutation

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.

These drug are given as an intravenous (IV) infusion, typically once every few weeks.

Using PDL-1 inhibitors to treat endometrial cancer

Durvalumab (Imfinzi) and avelumab (Bavencio) are drugs that target PDL-1, a protein related to PD-1 that is found on some tumor cells and immune cells. Blocking this protein can help boost the immune response against cancer cells. This can shrink some tumors or slow their growth.

Durvalumab can be given along with chemotherapy as an initial treatment option for advanced or recurrent endometrial cancer that has a defect in a mismatch repair gene (dMMR).  The chemo given with the PDL-1 inhibitor is usually carboplatin and paclitaxel.

Avelumab can be given alone after other drug treatments have been tried and if the cancer cells have been tested and found to have a high level of microsatellite instability (MSI-H) or a defect in a mismatch repair gene (dMMR).

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

Possible side effects of checkpoint inhibitors 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 but 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.