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Immunotherapy for Esophageal Cancer

Immunotherapy is the use of medicines that help a person’s own immune system find and destroy cancer cells more effectively. It can be used to treat some people with esophagus cancer.

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 “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 called immune checkpoint inhibitors target these checkpoint proteins, which can help restore the immune response against esophagus cancer cells.

PD-1 inhibitors

Pembrolizumab (Keytruda) and nivolumab (Opdivo) are drugs that target PD-1, a protein on T cells (a type of immune system cell). 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.

Pembrolizumab can be used to treat some advanced cancers of the esophagus or gastroesophageal junction (GEJ), typically when treatments such as surgery and chemoradiation (chemotherapy plus radiation therapy) can’t be done. Pembrolizumab might be given by itself or along with chemotherapy (and possibly the targeted drug trastuzumab, if the cancer tests positive for HER2), depending on the situation.

In certain cases when no other treatment options are available, this drug can be used for people whose cancer has tested positive for specific gene changes, such as a high level of microsatellite instability (MSI-H), defects in one of the mismatch repair genes (dMMR), or a high tumor mutational burden (TMB-H).

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

Nivolumab can be used in different situations:

  • It can be used in people with cancer of the esophagus or gastroesophageal junction (GEJ) who got chemotherapy and radiation (chemoradiation) before surgery, if lab tests after surgery show that some cancer may have been left behind.
  • It can be used by itself in people with advanced squamous cell cancer of the esophagus, typically after chemotherapy has been tried.
  • It can be used along with chemotherapy as a first treatment in people with advanced squamous cell cancer of the esophagus. When given this way, it can help some people live longer.
  • It can be used along with ipilimumab as a first treatment in people with advanced squamous cell cancer of the esophagus. When given this way, it can help some people live longer.
  • It can be used along with chemo in people with advanced adenocarcinoma of the esophagus or with advanced cancer of the gastroesophageal junction (GEJ).

This drug is given as an intravenous (IV) infusion, usually once every 2, 3, or 4 weeks.

CTLA-4 inhibitor

Ipilimumab (Yervoy) is another drug that boosts the immune response, but it has a different target. It blocks CTLA-4, another protein on T cells that normally helps keep them in check.

It can be used along with nivolumab as the first option to treat advanced squamous cell cancer of the esophagus that can’t be removed by surgery or that has spread to other parts of the body.

This drug is given as an intravenous (IV) infusion, usually once every 6 weeks when given in combination with nivolumab.

Possible side effects of immune checkpoint inhibitors

Common side effects of these drugs can include fatigue, cough, nausea, skin rash, poor appetite, constipation, muscle or joint pain, itching, fever, and diarrhea.

Other, more serious side effects happen 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 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 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.

More information about immunotherapy

To learn more about how drugs that work on the immune system are used to treat cancer, see Cancer Immunotherapy.

To learn about some of the side effects listed here and how to manage them, see Managing Cancer-related Side Effects.

The American Cancer Society medical and editorial content team

Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as editors and translators with extensive experience in medical writing.

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Ku GY and Ilson DH. Chapter 71 – Cancer of the Esophagus. In: Niederhuber JE, Armitage JO, Dorshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 6th ed. Philadelphia, Pa. Elsevier: 2020.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Esophageal and Esophagogastric Junction Cancers. V.4.2019. Accessed at on Jan 21, 2020.

Posner MC, Goodman KA, and Ilson DH. Ch 52 - Cancer of the Esophagus. In: DeVita VT, Hellman S, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology. 11th ed. Philadelphia, Pa: Lippincott-Williams & Wilkins; 2019. 

Last Revised: November 20, 2023

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