Immunotherapy
For Stomach Cancer

How is Immunotherapy Changing the Outlook for Patients with Stomach Cancer?

Reviewed by:

Joseph Chao, MD
City of Hope

Immunotherapy for stomach cancer, including checkpoint inhibitors and targeted antibodies, offer promising new treatment options for stomach (gastric) cancer patients.

While the number of people in the United States diagnosed with stomach cancer, or gastric cancer, is declining, this disease is the fifth most common cancer diagnosis worldwide and the third most deadly. About 90% to 95% of cancers of the stomach are adenocarcinomas. These cancers develop from the cells that form the innermost lining of the stomach. Other types of stomach cancer are gastrointestinal carcinoid tumors and gastrointestinal stromal tumors.

Untreated infection with bacteria called H. pylori is a potential cause of gastric cancer. Other stomach cancer risk factors may include smoking and a diet of highly processed or salty foods.

Worldwide, there are nearly one million new cases diagnosed each year and 780,000 deaths annually. In 2023, an estimated 26,000 people will be diagnosed with stomach cancer in the United States alone, in addition to roughly 11,000 deaths. This represents a substantive change since the very first estimates in 1975, when stomach cancer was the most common cancer. The reasons for this decline are not completely known, but may be linked to increased use of refrigeration for food storage.

In countries where stomach cancer is more common, public mass screenings for the disease have aided in diagnosing more cases during the disease’s early stages—when survival rates are drastically higher. When stomach cancer has metastasized, the 5-year survival rate falls to just 5%.

Stomach Cancer Treatment Options

Treatment of stomach cancer depends on where the disease initiated and the extent of its spread throughout the body. If diagnosed early, surgery is the first-line treatment for stomach cancer, sometimes in combination with chemotherapy and/or radiation treatment. For advanced stomach cancer, treatment aims to stabilize disease progression and improve patients’ prognosis.

Immunotherapy is class of treatments that take advantage of a person’s own immune system to help kill cancer cells. There are currently six FDA-approved immunotherapy options for stomach 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 stomach or gastroesophageal cancer
• Trastuzumab (Herceptin®): a monoclonal antibody that targets the HER2 pathway; approved for subsets of patients with advanced, HER2-positive gastroesophageal cancer
• Trastuzumab deruxtecan (Enhertu®): an antibody-drug conjugate that targets the HER2 pathway; approved for subsets of patients with advanced stomach or gastroesophageal cancer

Immunomodulators

• Dostarlimab (Jemperli): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced stomach 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 stomach or gastroesophageal cancer
• Pembrolizumab (Keytruda®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced stomach or gastroesophageal cancer

Several other immunotherapies—including checkpoint inhibitors, CAR T cell treatments, and multiple antibody approaches—are also being investigated in clinical trials and could soon provide stomach cancer patients with even more approved immunotherapy options.

CRI’s Impact in Stomach Cancer

• CRI researchers, including Lloyd J. Old, MD, and Sacha Gnjatic, PhD, analyzed cancer-testis (CT) antigen expression in gastric cancer and found that two CT antigens, NY-ESO-1 and MAGE-3, were expressed in 11.9% and 41.65%, respectively, in these cancers. Additionally, an immune response to NY-ESO-1 was detected in 6 out of 12 gastric cancer patients, indicating that it could potentially be a useful target for therapeutic vaccines.
• The CRI-SU2C Cancer Immunology Dream Team at Memorial Sloan Kettering Cancer Center, led by Michel Sadelain, MD, PhD, is taking a new approach to chimeric antigen receptor (CAR) T cell therapy in the lungs, and if proven to be successful, this approach can be extended to other mesothelin-expressing cancers, such as gastric cancer.
• Vladimir Vigdorovich, PhD, a CRI postdoctoral fellow at Albert Einstein College of Medicine, and colleagues developed a system to screen monoclonal antibodies directed at B7x (an immune checkpoint molecule) and found one that inhibited the growth of B7x-expressing tumors.

See what stomach cancer-specific research we’re currently funding. With your help, we can fund more research and revolutionize the way cancer is treated forever—curing more people and saving more lives.