Immunotherapy:
For Esophageal Cancer

How is Immunotherapy for Esophageal Cancer Changing the Outlook for Patients?

Reviewed by:

Samuel J. Klempner, MD
Dana-Farber / Harvard Cancer Center

Immunotherapy for esophageal cancer is being explored to reduce recurrence, as a first-line treatment, and in novel combinations for advanced stage cancer.

Two main types of cancer can affect the esophagus, a muscular tube through which food passes from the mouth to the stomach, as well as the gastroesophageal junction (GEJ):

• squamous cell carcinoma: cancer that begins in flat cells lining the esophagus
• adenocarcinoma: cancer that begins in cells that make and release mucus, which are usually associated with ectopic gastric mucosa

Esophageal cancer is three to four times more common in men than in women. Risk factors for esophageal cancer include smoking tobacco and heavy alcohol use as well as having acid reflux, which can inflame the cells of the esophagus and GEJ. Esophageal cancer is estimated to affect approximately 500,000 people globally each year. In the U.S. alone, there will be an estimated 19,000 new cases of esophageal cancer and 15,000 deaths in 2021. The five-year relative survival rate for patients with esophageal cancer is 43% for patients with localized disease found only in the esophagus; 23% for regional disease that has spread to nearby lymph nodes and organs; and 5% for metastatic disease that has spread to distant parts of the body.

Esophageal Cancer Treatment Options

When esophageal cancer is caught early, there are several effective therapies available, including endoscopic therapies, surgery, chemotherapy, and radiotherapy. Surgery remains the most common treatment for esophageal cancer, and surgery, chemotherapy, and radiation work well against localized cancers. Chemotherapy forms the backbone of therapy in patients with advanced or metastatic tumors.

Immunotherapy is class of treatments that take advantage of a person’s own immune system to help kill cancer cells. There are six FDA-approved immunotherapy options for esophageal cancer.

Targeted Antibodies

• Ramucirumab (Cyramza®): a monoclonal antibody that targets the VEGF/VEGFR2 pathway and inhibits tumor blood vessel growth; approved for subsets of patients with advanced gastroesophageal cancer
• Trastuzumab (Herceptin®): a monoclonal antibody that targets the HER2 pathway; approved for subsets of patients with advanced, HER2-positive gastroesophageal cancer, including as a first-line therapy
• Trastuzumab deruxtecan (Enhertu®): an antibody-drug conjugate that targets the HER2 pathway; approved for subsets of patients with advanced gastroesophageal cancer

Immunomodulators

• Dostarlimab (Jemperli): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced esophageal or gastroesophageal cancer that has DNA mismatch repair deficiency (dMMR)
• Nivolumab (Opdivo®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced esophageal or gastroesophageal cancer
• Pembrolizumab (Keytruda®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced esophageal or gastroesophageal cancer

Immunotherapy research on esophageal cancer is ongoing and holds the promise of new treatment options. Several other immunotherapy approaches for esophageal cancer have shown promise in early clinical trials.

CRI’s Impact in Esophageal Cancer

Immunotherapy has the potential to improve the outlook for patients and families affected by the disease and bring us ever closer to effective, lasting cures for esophageal cancer.

• CRI researchers analyzed NY-ESO-1 cancer-testis (CT) antigen expression in esophageal cancer and have sought to correlate this expression with disease stage and clinical outcome (high expression frequency indicates a feasible vaccine target).
• Clinical investigator Eiichi Nakayama, MD, and colleagues at Okayama University Graduate School of Medicine and Dentistry in Japan reported in the International Journal of Cancer that a vaccine composed of the NY-ESO-1f long peptide administered with the immune stimulants Montanide ISA-51 and Picibanil OK-432 could elicit integrated immune responses including antibodies, CD4+ helper T cells, and CD8+ killer T cells in nine out of the ten patients enrolled in a phase I clinical trial.

Explore CRI’s current funding for esophageal cancer research in our funding directory.