Targeted 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 if chemo is no longer working.

Trastuzumab

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.

Trastuzumab (Herceptin) is a drug that targets the HER2 protein. It may help treat these cancers when used along with chemotherapy. If you have esophageal 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 the HER2 protein or gene are very unlikely to be helped by this drug.

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

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.

Ramucirumab

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 (Cyramza) 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 (the GE junction is the place where the stomach and esophagus meet). 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 and Larotrectinib

Some tumors have genes that join together. One of those genes, called NTRK, can combine (fuse) with other genes. The fusion of these genes leads to abnormal growth of cells and can turn into cancer. Two drugs that target this abnormal gene pattern (also called a NRTK gene fusion) are entrectinib (Rozlytrek) and larotrectinib (Vitrakvi). They might be given to people with metastatic esophageal cancer or esophageal cancer that cannot be removed with surgery, who have this NTRK gene fusion, and whose tumors have grown while on 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.

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.

The American Cancer Society medical and editorial content team

Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

Amatu A, Sartore-Bianchi A, Siena S. NTRK gene fusions as novel targets of cancer therapy across multiple tumour types. ESMO Open. 2016;1(2):e000023. Published 2016 Mar 18. doi:10.1136/esmoopen-2015-000023.

Ku GY and Ilson DH. Chapter 71 – Cancer of the Esophagus. In: Niederhuber JE, Armitage JO, Dorshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 6th ed. Philadelphia, Pa. Elsevier: 2020.

National Cancer Institute. Physician Data Query (PDQ)-Health Professional Version. Esophageal Cancer Treatment. 2019. Accessed at https://www.cancer.gov/types/esophageal/hp/esophageal-treatment-pdq on Jan 21, 2020.

National Cancer Institute. Physician Data Query (PDQ)-Patient Version. Esophageal Cancer Treatment. 2019. Accessed at https://www.cancer.gov/types/esophageal/patient/esophageal-treatment-pdq#_159 on Jan 21, 2020.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Esophageal and Esophagogastric Junction Cancers. V.4.2019. Accessed at www.nccn.org/professionals/physician_gls/pdf/esophageal.pdf on Jan 30, 2020.

Posner MC, Goodman KA, and Ilson DH. Ch 52 - Cancer of the Esophagus. In: DeVita VT, Hellman S, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology. 11th ed. Philadelphia, Pa: Lippincott-Williams & Wilkins; 2019.

References

Amatu A, Sartore-Bianchi A, Siena S. NTRK gene fusions as novel targets of cancer therapy across multiple tumour types. ESMO Open. 2016;1(2):e000023. Published 2016 Mar 18. doi:10.1136/esmoopen-2015-000023.

Ku GY and Ilson DH. Chapter 71 – Cancer of the Esophagus. In: Niederhuber JE, Armitage JO, Dorshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 6th ed. Philadelphia, Pa. Elsevier: 2020.

National Cancer Institute. Physician Data Query (PDQ)-Health Professional Version. Esophageal Cancer Treatment. 2019. Accessed at https://www.cancer.gov/types/esophageal/hp/esophageal-treatment-pdq on Jan 21, 2020.

National Cancer Institute. Physician Data Query (PDQ)-Patient Version. Esophageal Cancer Treatment. 2019. Accessed at https://www.cancer.gov/types/esophageal/patient/esophageal-treatment-pdq#_159 on Jan 21, 2020.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Esophageal and Esophagogastric Junction Cancers. V.4.2019. Accessed at www.nccn.org/professionals/physician_gls/pdf/esophageal.pdf on Jan 30, 2020.

Posner MC, Goodman KA, and Ilson DH. Ch 52 - Cancer of the Esophagus. In: DeVita VT, Hellman S, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology. 11th ed. Philadelphia, Pa: Lippincott-Williams & Wilkins; 2019.

Last Medical Review: March 20, 2020 Last Revised: March 20, 2020

American Cancer Society medical information is copyrighted material. For reprint requests, please see our Content Usage Policy.