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As researchers have learned more about the changes in cells that cause cancer, they have developed newer drugs that specifically target these changes. Targeted drugs work differently from standard chemotherapy drugs. They sometimes work when standard chemo drugs don’t, and they often have different side effects. They can be used either along with chemo or by themselves.

Drugs that target HER2

Some esophagus cancers have too much of the HER2 protein on the surface of their cells, which can help cancer cells grow. Having too much of this protein is caused by having too many copies of the HER2 gene. Cancers with increased levels of HER2 are called HER2-positive. Drugs that target the HER2 protein can often be helpful in treating HER2-positive cancers.

Trastuzumab (Herceptin, others)

Trastuzumab is a monoclonal antibody, a man-made version of an immune system protein, which targets HER2. It can be used to help treat some HER2-positive cancers of the gastroesophageal (GE) junction (the place where the esophagus and stomach meet).

If you have a GE junction cancer and can’t have surgery, your doctor may have your tumor tested for the HER2 protein or gene. People whose cancers have normal amounts of HER2 are very unlikely to be helped by this drug.

Trastuzumab is given into a vein (IV), typically once every 3 weeks, along with chemo.

Herceptin was the original brand name for trastuzumab, but several similar versions (called biosimilars) are now available as well, including Ogivri, Herzuma, Ontruzant, Trazimera, and Kanjinti.

Possible side effects of trastuzumab

Most of the side effects of trastuzumab are relatively mild and can include fever and chills, cough, and headache. These occur less often after the first dose.

This drug can also sometimes cause heart damage, leading to the heart muscle becoming weak. This drug is not given with certain chemo drugs called anthracyclines, such as epirubicin (Ellence) or doxorubicin (Adriamycin), because it can further increase the risk of heart damage if they are given together. Before starting treatment with this drug, your doctor may test your heart function with an echocardiogram or a MUGA scan.

Fam-trastuzumab deruxtecan (Enhertu)

This is an antibody-drug conjugate (ADC), which is a monoclonal antibody linked to a chemotherapy drug. In this case, the anti-HER2 antibody acts like a homing signal by attaching to the HER2 protein on cancer cells, bringing the chemo directly to them.

This ADC can be used by itself to treat advanced HER2-positive GE junction cancers, typically after treatment with trastuzumab has been tried.

This drug is infused into a vein (IV). It is typically given once every 3 weeks.

Side effects of fam-trastuzumab deruxtecan

This drug can cause low blood cell counts, which can increase a person’s risk of infections and bleeding. Other common side effects can include nausea, vomiting, diarrhea or constipation, loss of appetite, fever, feeling tired, and hair loss.

This drug can cause serious lung disease in some people, which might even be life threatening. It’s very important to let your doctor or nurse know right away if you’re having symptoms such as coughing, wheezing, trouble breathing, or fever.

This drug can also rarely cause heart damage. Before starting treatment with this drug, your doctor may test your heart function with an echocardiogram or a MUGA scan.

Ramucirumab (Cyramza)

For cancers to grow and spread, they need to make new blood vessels so that the tumors get blood and nutrients. One of the proteins that tells the body to make new blood vessels is called VEGF. To start this process, VEGF attaches to other proteins on the outside of the cancer cell called receptors.

Ramucirumab is a monoclonal antibody that blocks the process of making new blood vessels. Ramucirumab joins to the VEGF receptor, which blocks VEGF and stops the signal to the body to make more blood vessels. This can help slow or stop the growth of the cancer.

Ramucirumab is used to treat cancers that start at the gastroesophageal (GE) junction when they are advanced. It is most often used after another drug stops working. It can be used alone or in combination with the chemo drug paclitaxel.

This drug is given as infusion into a vein (IV) every 2 weeks.

Possible side effects of ramucirumab

The most common side effects of this drug are high blood pressure, swelling of the arms or legs, protein in the urine, and fatigue. Rare but possibly serious side effects include blood clots, severe bleeding, holes forming in the stomach or intestines (called perforations), and problems with wound healing. If a hole forms in the stomach or intestine it can lead to severe infection and may require surgery to correct.

Entrectinib (Rozlytrek) and Larotrectinib(Vitrakvi)

In some cancers, the cells have genes that join together. The fusion of one of these genes, called NTRK, with another gene can lead to abnormal cell growth.

Drugs that target this abnormal gene fusion, called TRK inhibitors, include entrectinib and larotrectinib. One of these drugs might be used to treat esophageal cancer with an NTRK gene fusion if the cancer cannot be removed with surgery or has spread to other parts of the body, and if it has grown despite other treatments.

These drugs are given as pills daily.

Possible side effects of entrectinib and larotrectinib

The most common side effects are fatigue, nausea, vomiting, dizziness, cough, diarrhea, and constipation. Other more serious, but less common, side effects include liver problems and confusion.

Zolbetuximab (Vyloy)

Zolbetuximab is a monoclonal antibody , a man-made version of an immune system protein, that targets claudin 18.2 (CLDN18.2). Claudin 18.2 is a protein that is found between normal epithelial cells and plays an important role in keeping these cells bound together. When an epithelial cell transforms into a cancer cell, however, claudin 18.2 may be found on the surface of these cancer cells.
 

If you have a GE junction cancer that is HER2-negative, and can’t have surgery, your doctor may have your tumor tested for the CLDN18.2 protein. Drugs that target the CLDN18.2 protein can be helpful in treating cancers that express high amounts of CLDN18.2 on their cell surface.
 

Zolbetuximab is given into a vein (IV), typically once every 2 to 3 weeks, along with chemo.

Possible side effects of zolbetuximab

The most common side effects are nausea, vomiting, diarrhea, fatigue, decreased appetite, stomach pain, weight loss, constipation, and decreased sensation in fingertips/toes (also called sensory neuropathy). Other more serious, but less common, side effects include low blood cell counts, which can increase a person’s risk of infections and bleeding; liver problems; and changes in electrolyte levels, such as sodium, phosphate, potassium, and magnesium.