Advanced Esophageal Cancer and Immunotherapy

Jennifer Welsh
·11 min read

A Newer Treatment Option

Medically reviewed by Gagandeep Brar, MD

Immunotherapy for esophageal cancer is a newer treatment approach shown to improve the survival of specific people. Immunotherapy is used to prime or kick-start the immune system's fight against cancer. For esophageal cancer (cancer in the tube that connects your throat to your stomach), it's used in certain stage 2, 3, and 4 cancers to extend life.

This article will review the immunotherapy treatment options for esophageal cancer, including Opdivo (nivolumab), Keytruda (pembrolizumab), and Yervoy (Ipilimumab), and their impact on life expectancy and survival rate for esophageal cancer. It will cover immunotherapy's benefits and side effects for esophageal cancer and how to get it.

How Immunotherapy Targets Esophageal Cancer

Immunotherapy for cancer works by priming the body’s immune system to fight off the cancer cells.

Immunotherapy drugs for esophageal cancer are immune checkpoint inhibitors. They essentially take the brakes off the immune system. Your body has built-in checkpoints—proteins on immune system cells that help stop them from attacking normal cells. Cancer cells sometimes take advantage of these blocks to grow without being destroyed by the body.

These proteins act as switches that can turn an immune system reaction on or off. Immune checkpoint inhibitors turn these switches off to allow the immune system to fight cancer cells.

Specifically, immune checkpoint inhibitors for esophageal cancer work on two different switches, as follows:

  • They block PD-1, a protein on T cells (a type of immune cell) that usually keeps them from attacking other cells in the body. PD-1 binds to PD-L1 on some cancer cells, stopping the T cell from killing the cancer cell. By blocking this binding, PD-1 inhibitors allow the T cell to kill the cancer.

  • They block CTLA-4, another protein on T cells that helps keep them in check. CTLA-4 binds to a protein called B7 on cancer cells, stopping the T cell from killing the cancer. By blocking this binding, CTLA-4 inhibitors allow the T cells to kill the tumor cells.



Immunotherapy

The immune system is a complex set of systems in the body. It is essential in keeping us healthy. Immunotherapy is complex and can cause severe adverse reactions by over-activating the immune system. Because of this, its use has been controversial.



Immunotherapy's Effect on Esophageal Cancer Life Expectancy

When people with advanced esophageal cancer were taking immunotherapy Opdivo or Keytruda in clinical trials, it took longer for their cancer to get worse compared to people taking traditional treatments. In some studies, they also lived longer overall.

Immunotherapies have been tested in cancers of the esophagus and those of the gastroesophageal junction, where the esophagus meets the stomach. They've also been tested on different types of esophageal cancer, such as:

  • Adenocarcinomas start in the glands that lubricate the esophagus and are more common at the gastroesophageal junction.

  • Squamous cell carcinomas start in the lining of the esophagus and are more common in the upper and middle of the esophagus.

In a clinical trial comparing Keytruda and chemotherapy to placebo (an inactive substance) and chemotherapy, people with locally advanced or metastatic esophageal or gastroesophageal junction cancer who got the immunotherapy lived on average 12.4 months, compared with 9.8 months. Their tumors were also slower to progress.

This immunotherapy was even more effective on patients with esophageal squamous cell carcinoma with a high level of PD-L1: They lived 13.9 months vs. 8.8 months.

A clinical trial of Opdivo recruited people with stages 2 or 3 esophageal or gastroesophageal junction cancer and residual disease after surgery. Those who got the immunotherapy immediately after surgery lived 22.4 months without their cancer worsening, compared with 11 months for those who received a placebo.

These results were more pronounced in people with squamous cell cancer, who lived an average of 29.7 months without worsening.

Types of Esophageal Cancer Immunotherapy

The immunotherapy drugs approved for esophageal cancer include:

  • Opdivo (nivolumab) is used for esophagus or gastroesophageal junction cancers. These include advanced squamous cell cancer and advanced adenocarcinomas.

  • Keytruda (pembrolizumab) treats advanced cancers of the esophagus or gastroesophageal junction, people whose cancer has tested positive for specific gene changes, and people with advanced gastroesophageal junction cancers positive for human epidermal growth factor receptor 2 (HER2), a receptor that promotes cell growth and division.

  • Yervoy (ipilimumab) is often used with Opdivo as the first option to treat some instances of advanced squamous cell cancer of the esophagus. In these cases, the tumor is either inoperable or has spread.

Immunotherapy is currently approved to treat certain stages of esophageal cancer. Stages 2 and 3 esophageal cancers that can’t be removed with surgery may be treated with immunotherapy or chemotherapy.



Neoadjuvant vs. Adjuvant Treatment

When multiple therapies are used in the treatment process, the sequence of therapies matters. Therapies can be given before or after surgery. They can also be given together at the same time.

Neoadjuvant cancer therapies are used before surgery to shrink the tumor and make the operation easier. Adjuvant cancer therapies are used after initial primary treatment—either radiation or surgery—to help prevent cancer from returning.



Stage 4 esophageal cancer has spread to other major organs and tissues in the body. People with stage 4 esophageal cancers may be treated with combination therapy of immunotherapy, chemotherapy, radiation, or targeted drugs.

In these cases, Opdivo may be used as adjuvant therapy, or Keytruda and Yervoy may be used as primary treatment. Another option is Keytruda with chemotherapy. These combinations are used in different cases.

Another case in which immunotherapy would be used to treat esophageal cancer is when it comes back after previous treatments. Recurrent esophageal cancer may be treated with immunotherapies Opdivo and Yervoy or Opdivo with chemotherapy.

Side Effects of Immunotherapy

Side effects of immunotherapy for esophageal cancer include:

  • Fever and fatigue

  • Cough

  • Intestinal distress, including nausea, poor appetite, constipation, or diarrhea

  • Skin rash or itching

  • Muscle or joint pain

More serious complications can also happen after an immunotherapy infusion. Tell your healthcare provider if you start feeling these symptoms:

  • Fever and chills

  • Facial flushing (turning red)

  • Itchy skin with or without a rash

  • Dizziness

  • Wheezing and trouble breathing

These drugs interfere with your body’s natural process for stopping immune overreactions. So, it’s possible they can cause autoimmune reactions, in which the immune system starts attacking the body. This can lead to severe or even life-threatening problems.

Autoimmune reactions may impact organs, including the:

  • Lungs

  • Intestines

  • Liver

  • Hormone glands

  • Kidneys

  • Skin

What Happens During Immunotherapy for Esophageal Cancer

Many immunotherapy drugs are given as intravenous (IV) infusions directly into a vein. Often people getting cancer treatment will have a port or peripherally inserted central catheter (PICC) line implanted to make the treatment process more accessible.

Infusions can be given through these medical devices, so healthcare providers don’t need to insert an IV line into your arm or hand every time you get treatment. This will be inserted during an earlier procedure before your treatment starts.

Infusions typically happen at an infusion clinic, healthcare provider’s office, or outpatient unit. They’re usually given on a set schedule, such as:

  • Opdivo (nivolumab) is given once every two, three, or four weeks, and the infusion takes 30 minutes.

  • Keytruda (pembrolizumab) is typically given every three or six weeks; the infusion takes 30 minutes.

  • Yervoy (Ipilimumab) is given with nivolumab, usually once every six weeks, and the infusion takes 30 minutes.

During and after your infusion, healthcare professionals will watch you closely for any reactions. Tell them immediately if you start having chills or shaking, itching, rash, flushing, difficulty breathing, dizziness, fever, and feeling faint.

Self-Care When on Immunotherapy

Taking care of your body is important for immunotherapy and cancer treatments, which can be achieved in several different ways. First, talk to your healthcare provider if you have any symptoms or side effects from the medication, even if you think they aren't relevant or related. Discuss any changes in your health with your care team.

While you’re on immunotherapy, you may have some digestive distress. There are steps you can take to make this better, including:

  • Avoid caffeine and alcohol.

  • Avoid hot, spicy foods.

  • Stay away from overly sweet or greasy foods.

  • Drink lots of water and other clear liquids.

  • Eat small, frequent meals—try splitting your food intake into six to eight smaller meals.

  • Eat dry foods such as crackers or dry cereal.

While you’re getting cancer treatment, try as best you can to eat a healthy diet. Focus on fruits and veggies, low-fat foods, and protein-rich snacks. Avoid high-fat animal products and salty foods.

You may be feeling extra tired because of the immunotherapy. Eating enough healthy foods can help you keep your weight up and your muscles strong, which can fend off fatigue. Listen to your body and get as much rest as you need. Ask your friends and family to pitch in so you can take a break.

When you feel up to it, get some light exercise, which can help with your symptoms of fatigue and nausea. Start slowly with gentle activity such as walking, just for short periods. Make sure to stay hydrated and rest when needed. Take this opportunity to get active with things you enjoy—exercise shouldn’t be a chore.

Follow-Up Visits With Your Oncologist

While getting cancer treatment, you’ll have regular appointments with your oncologist (cancer specialist) and care team. They’ll do tests to determine if the treatment is working. Come prepared with a list of any new medications you’re taking and side effects or symptoms you're experiencing.

Here are some potential questions you may want to ask your oncologist:

  • Am I at risk for infections?

  • Are there any foods I should avoid to not get an infection?

  • Is it OK to be in a crowd of people? Do I have to wear a mask?

  • Can I have visitors over? Do they need to wear a mask?

  • Am I at risk for bleeding? What should I do if I cut myself or start bleeding?

  • Are there any medicines I should not take?

  • Are there any other medicines I should keep on hand?

  • What over-the-counter (OTC) medicines am I allowed to take?

  • Are there any vitamins and supplements I should or should not take?

  • Do I need to use birth control? What should I do if I want to get pregnant in the future?

  • What should I do if I get a rash?

  • If my skin or eyes are itchy, what can I use to treat this?

  • What can I do about my fatigue?

  • When should I call a healthcare provider?

When getting immunotherapy, see your healthcare provider regularly and follow through with any testing they order. They may order tests to check if your body and the cancer are responding to immunotherapy. They’ll also likely order some lab tests before you begin your treatment to see if immunotherapy suits you.

During cancer treatment, list your prescriptions, any OTC medicines, and vitamins, minerals, or other dietary supplements you are taking. Make sure all of your healthcare providers are aware of these medications and supplements.

If immunotherapy is causing side effects or not working the way your oncologist had hoped, you can ask about new types of treatment for esophageal cancer that are being tested in clinical trials.

These include targeted therapies that attack cancer cells based on features specific to the cancer. These treatments aim to kill cancer cells, block their growth, or keep them from spreading. One targeted treatment for esophageal cancer is trastuzumab, a monoclonal antibody that blocks the protein HER2, which sends growth signals to esophageal cancer cells.

Summary

Immunotherapy is a newer type of treatment for esophageal cancer. It seems to improve survival rates for certain patients. Oncologists use immunotherapy in some patients with stages 2, 3, and 4 esophageal cancers.

Immunotherapy options for esophageal cancers include Opdivo (nivolumab), Keytruda (pembrolizumab), and Yervoy (Ipilimumab). Immunotherapy boosts the body's immune system. These drugs target immune checkpoints to kill cancer.

In trials, Opdivo and Keytruda (sometimes used with Yervoy) extend disease-free survival in patients with advanced esophageal cancer.

Your care team will give you this drug through an IV in a clinic or medical office. The process lasts around 30 minutes. They'll watch you during and after infusions.

Oncologists may use immunotherapy alone or with other treatments. These include chemotherapy, radiation, or targeted drugs. Some locally advanced, metastatic, or recurrent esophageal cancer patients may get immunotherapy.

Immunotherapy side effects include fever, fatigue, digestive issues, and skin rash. It can also cause more severe reactions.

Keeping a healthy lifestyle and talking to your care team is vital during immunotherapy. Talk to your oncologist about side effects. Other new treatments include targeted therapies like trastuzumab or clinical trials.