Targeted Drug Therapy for Esophageal Cancer
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 (esophageal) 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 and other brand names) 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 junction (GEJ), which is the place where the esophagus and stomach meet.
If you have a GEJ cancer and can’t have surgery, your doctor may have your cancer cells tested for the HER2 protein or gene. People whose cancer cells 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.
Possible side effects of trastuzumab
Side effects of trastuzumab can include fever and chills, cough, and headache. These tend to occur less often after the first dose.
This drug can also sometimes cause heart damage. Before starting treatment with this drug, your doctor may test your heart function with an echocardiogram or a MUGA scan.
This is an antibody-drug conjugate (ADC), which is a monoclonal antibody (a man-made version of an immune system protein) linked to a chemotherapy drug. In this case, the anti-HER2 antibody acts like a homing device, attaching to the HER2 protein on cancer cells and bringing the chemo directly to them.
This ADC can be used by itself to treat advanced HER2-positive GEJ 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.
Possible 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, 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.
Drugs that target VEGFR
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 vascular endothelial growth factor (VEGF). To start this process, VEGF attaches to a protein on the outside of the cancer cell called a VEGF receptor (VEGFR).
Ramucirumab (Cyramza) is a monoclonal antibody, a man-made version of an immune system protein, that that attaches to the VEGFR. It 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 GEJ cancers when they are advanced. It is most often used after another drug stops working. It can be used alone or in combination with chemo.
This drug is given as an infusion into a vein (IV), typically 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.
Drugs that target claudin 18.2 (CLDN18.2)
Claudin 18.2 (CLDN18.2) is a protein that normally helps epithelial cells stay bound together. Esophageal cancer cells sometimes have too much of this protein on their surface.
Zolbetuximab (Vyloy) is a monoclonal antibody, a man-made version of an immune system protein, that targets CLDN18.2.
If you have a GEJ cancer that is HER2-negative and you can’t have surgery, your doctor may have your cancer cells tested to see if they have high amounts of CLDN18.2 on their surface to show if you might be helped by this drug.
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, belly pain, weight loss, constipation, and decreased sensation in fingertips/toes (sensory neuropathy).
More serious but less common side effects can 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.
Drugs that target cells with NTRK gene changes
In a small number of esophageal cancers, the cells have changes in one of the NTRK genes. This causes them to make abnormal TRK proteins, which can lead to abnormal cell growth and cancer.
Larotrectinib (Vitrakvi),entrectinib (Rozlytrek),andrepotrectinib (Augtyro) are drugs that target the TRK proteins, so they are called TRK inhibitors. These drugs can be used to treat advanced cancers with NTRK gene changes that are still growing despite other treatments.
These drugs are taken as pills or a liquid, once or twice daily.
Possible side effects of TRK inhibitors
Common side effects of these drugs can include dizziness, fatigue, nausea, vomiting, constipation, weight gain, and diarrhea.
Less common but serious side effects can include abnormal liver tests, increased risk for fractures, heart problems, vision changes, and confusion.
Other targeted therapy drugs
Some other targeted drugs might be useful in certain circumstances. For example:
- Selpercatinib (Retevmo), a drug that targets the RET protein, can be used to treat advanced cancers with RET gene changes that are still growing despite other treatments.
- Dabrafenib (Tafinlar) and trametinib (Mekinist) might be an option to treat cancers with a BRAF gene change known as a V600E mutation.
More information about targeted therapy
To learn more about how targeted drugs are used to treat cancer, see Targeted Cancer Therapy.
To learn about some of the side effects listed here and how to manage them, see Managing Cancer-related Side Effects.
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- References
Developed by the American Cancer Society medical and editorial content team with medical review and contribution by the American Society of Clinical Oncology (ASCO).
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Last Revised: August 14, 2025
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