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Patient undergoing esophageal cancer immunotherapy

A part of the digestive system, the esophagus is a hollow, muscular tube through which food passes from the throat to the stomach. Esophageal cancer is a relatively uncommon and often aggressive malignancy that makes up approximately 1% of all cancer cases in the United States. The most common types are squamous cell carcinoma, which originates in the cells that line the esophagus, and adenocarcinoma, which originates in the cells that produce and release mucus.

Surgery has traditionally been the main form of treatment for esophageal cancer, but immunotherapy is now a promising alternative for some patients. Unlike surgery and chemotherapy, this groundbreaking treatment does not act directly on cancerous cells. Instead, it capitalizes on the power of the body’s own immune system to fight cancer.

When might a doctor recommend immunotherapy as a treatment option for esophageal cancer?

Used either alone or along with chemotherapy, immunotherapy became a standard treatment for some types of esophageal cancer after the U.S. Food and Drug Administration (FDA) approved several drugs and drug combinations:

  • In 2019, the FDA approved the use of pembrolizumab (Keytruda®) as a second-line treatment for some patients with locally advanced or metastatic esophageal squamous cell carcinoma.
  • In 2022, the FDA approved the use of nivolumab (Opdivo®) in combination with fluoropyrimidine- or platinum-based chemotherapy as a first-line treatment for some patients with advanced or metastatic esophageal squamous cell carcinoma.
  • In 2022, the FDA approved the use of Opdivo® in combination with the immune checkpoint inhibitor ipilimumab (Yervoy®) as a first-line treatment for some patients with advanced or metastatic esophageal squamous cell carcinoma.

Benefits of immunotherapy for esophageal cancer

Oftentimes, esophageal cancer does not produce noticeable symptoms until it has progressed to an advanced stage and invaded other organs and tissues. If the cancer is widespread, a surgeon may not be able to remove all of it with surgery. In this situation, the first-line treatment was previously chemotherapy, a long-established systemic treatment that can potentially shrink some advanced esophageal tumors. However, the cancer may still worsen and continue to spread. Also, because chemo drugs indiscriminately destroy rapidly dividing cells, the treatment invariably damages some healthy cells along with the cancerous cells. This can lead to side effects such as nausea, vomiting, mouth sores and hair loss. For these reasons and others, immunotherapy may be a better option for some patients.

Another key benefit of immunotherapy is that it offers the possibility of long-term esophageal cancer control. After it “teaches” the immune system to “remember” cancerous cells, the resulting “immunomemory” can help ensure lasting protection against a cancer recurrence, even long after the treatment ends.

Side effects of immunotherapy for esophageal cancer

Compared to chemotherapy, immunotherapy is usually easier on the body, but it is not without side effects. Sometimes, it may trigger an overly robust immune response, which can cause inflammation throughout the body and other immune-related adverse events, such as:

  • Weakness and fatigue
  • Joint and muscle pain 
  • Loss of appetite 
  • Constipation or diarrhea 
  • Coughing and shortness of breath 
  • Itchy skin rash 
  • Nausea 
  • Fever 

While most side effects of immunotherapy are relatively mild and short-lived, some are potentially serious and warrant immediate medical attention. It is important to discuss any side effects with a physician, who may pause the immunotherapy, prescribe an immunosuppressant to tone down the immune response or suggest other ways to manage the associated side effects.

Immunotherapy vs. chemotherapy for esophageal cancer

Immunotherapy and chemotherapy are both potentially effective cancer treatments. The main difference between them is the way they fight cancer. Chemotherapy uses powerful drugs to target and destroy rapidly dividing cells throughout the body. Immunotherapy bolsters the body’s immune system to that it is better able to recognize and attack cancerous cells.

Effectiveness of immunotherapy for esophageal cancer

Many factors can influence the effectiveness of cancer treatment, including the type, location and stage of the tumor and the patient’s overall health. For some patients with esophageal cancer, immunotherapy may work better than chemotherapy.

According to the results of a large clinical trial, two immunotherapy-based combination therapies proved to be more effective than chemotherapy alone for some patients with advanced or metastatic esophageal cancer that could be surgically treated. The combination therapies evaluated in the trial were Opdivo® plus chemotherapy and Opdivo® plus Yervoy®.

How Moffitt Cancer Center approaches immunotherapy for esophageal cancer

Moffitt is proud to offer the latest treatment options for esophageal cancer, including FDA-approved immunotherapies and promising new options available only through our robust clinical trials program. A recognized leader in cancer research, Moffitt has earned the prestigious Comprehensive Cancer Center designation from the National Cancer Institute. We are committed to improving outcomes and quality of life for patients with esophageal cancer, and we gain more ground every day.

If you would like to learn more about immunotherapy for esophageal cancer, you are welcome to talk with a specialist in the Gastrointestinal Oncology Program at Moffitt. You can request an appointment with or without a referral; simply call 1-888-663-3488 or submit a new patient registration form online.