Esophageal Cancer: Targeted Therapy

Targeted therapy medicines attack certain proteins or cell functions that help cancer cells grow. Like chemotherapy (chemo), these medicines work throughout the body. But they work in different ways. These medicines mainly target cancer cells, so the side effects are different and often less severe than those from chemo.

Cancer cells are tested to see if they have the genes, proteins, or other factors that these medicines target. This helps your doctor know if and which targeted therapy can help.

At this time, these targeted medicines are approved for use to treat certain esophageal cancers:

• Trastuzumab targets the HER2 protein. HER2 is found on the surface of cells and can help them grow faster. Blocking HER2 slows cell growth.
• Ramucirumab targets VEGF receptors and works by blocking new blood vessel growth around a tumor. Tumors need new vessels to get the blood and nutrients they need to grow beyond a certain size. Blocking this can help slow or stop the growth of the cancer.
• Entrectinib and larotrectinib target a fusion gene called NTRK. Blocking this gene can slow cancer cell growth.

Targeted therapy isn't part of the main treatment for most people with esophageal cancer. It works only if the cancer cells have the changes that the medicine targets. It is most often used to treat some esophageal cancers that start at the place where the esophagus meets the stomach (the gastroesophageal junction or GEJ).

Here are some common uses:

• Trastuzumab can be used along with chemo as first-line treatment in people with advanced GEJ cancers that make the HER2 protein.
• Ramucirumab can be used (either alone or with chemo) in people with advanced GEJ cancers who have had at least one earlier treatment that didn't work.
• Entrectinib or larotrectinib might be used if the cancer cells have the NTRK gene fusion and the cancer can't be removed with surgery, has spread to other parts of the body, or is growing even though other treatments have been tried.

Before treatment starts, you'll meet with a medical oncologist. This is a doctor who specializes in treating cancer with medicines. They will discuss your treatment choices with you and explain what you might expect.

Trastuzumab and ramucirumab are given as an infusion into your blood through a vein (I.V., or intravenous). In most cases, you'll get it once every 2 or 3 weeks in an outpatient setting. This means that you get it at a hospital, clinic, or health care provider's office. Then you can go home after treatment. Rarely, you may need to stay in the hospital during treatment.

Entrectinib and larotrectinib are pills that you take at home.

Your doctor will watch you for reactions during the treatments. Since each I.V. treatment may last for a while, you may want to take along something that's comforting to you, such as music to listen to. You may also want to bring something to keep you busy, like a book or mobile device.

Side effects of targeted therapy depend on which type of medicine you're taking. Ask your doctor for more details about possible side effects. Tell your doctor about any changes or side effects you have. There are often things that can be done to help you feel better. In most cases, side effects start going away within a few weeks after treatment ends.

Some of the side effects from trastuzumab include:

• Allergic reactions during the infusion, such as fever, chills, nausea, and headache. If you have a reaction, it will likely be short-term and treatable. Reactions most often happen with the first dose. Your doctor will then decide if you can continue to get this medicine.
• Heart damage. This most often happens when this medicine is given along with certain chemo medicines. Before treatment, your doctor might check your heart function.

Some of the possible side effects from ramucirumab include:

• Allergic reactions during the infusion. If you have a reaction, it will likely be short-term and treatable. Your doctor will decide if you can continue to get this type of medicine.
• High blood pressure. This may need to be treated with medicine.
• Protein in your urine.
• Swelling in your arm or leg.
• Diarrhea.
• Headache.
• Low white blood cell counts. This can increase your risk of infection.
• Feeling achy and tired.
• Increased chance of blood clotting. This raises your risk of heart attack and stroke. Tell your doctor right away if you have chest pain, shortness of breath, numbness, or weakness, or if you feel dizzy or faint.
• Low platelet counts. This can lead to easy bruising and bleeding. Tell your doctor right away if you cough up blood, have blood in stools or urine, or have bleeding from your nose or gums.
• Holes forming in the stomach or intestines.

Some of the possible side effects from entrectinib or larotrectinib include:

• Extreme tiredness (fatigue).
• Nausea and vomiting.
• Diarrhea.
• Constipation.
• Dizziness.
• Confusion.
• Cough.
• Liver problems.
• Weight gain.
• A risk for fractures.
• Vision changes.
• Heart problems.

It's important to know which medicines you're taking. Write down the names of your medicines. Ask your health care team how they work, what they're for, and what side effects they might have.

Talk with your health care providers about what side effects to watch for and when to call them. Make sure you know what number to call with questions. Is there a different number to call after office hours or on holidays and weekends?

It may be helpful to keep a diary of your side effects. A written list can make it easier for you to remember your questions when you go to your appointments. It will also make it easier for you to work with your healthcare team to make a plan to manage your side effects.