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Targeted therapy drugs treat cancer by targeting specific features, changes, mutations, or substances in or on cancer cells. They are designed to stop cancer cells from growing and spreading while limiting damage to normal, healthy cells.

Targeted therapy can sometimes be used to treat stomach cancer (gastric cancer), either alone or along with chemo, depending on the situation.

Drugs that target HER2

In some people with stomach cancer, the cancer cells have too much HER2 protein on their surface, which helps the cells grow. Cancers with increased levels of HER2 are called HER2-positive. Drugs that target the HER2 protein can often be helpful in treating these cancers.

These drugs only work if the cancer cells have too much HER2, so samples of the cancer must be tested for HER2 before starting treatment (see Tests for Stomach Cancer).

Trastuzumab (Herceptin and other brand names)

Trastuzumab is a monoclonal antibody, a lab-made version of an immune system protein, which targets HER2. Adding trastuzumab to chemo can help some people with advanced, HER2-positive stomach cancer live longer than with just chemo alone.

Trastuzumab is infused into a vein (through an IV line or central venous catheter). It is typically given once every 2 or 3 weeks with chemo.

Side effects of trastuzumab

Side effects of trastuzumab can include fever and chills, weakness, nausea, vomiting, cough, diarrhea, and headache. These tend to occur less often after the first dose.

This drug also rarely can cause heart damage. The risk is higher if trastuzumab is given with certain chemo drugs called anthracyclines, such as epirubicin. 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 device 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 stomach cancer, typically after treatment with trastuzumab has been tried.

This drug is infused into a vein (through an IV line or central venous catheter). It is typically given 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 also rarely can 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 tumors to grow, they need to make new blood vessels to get blood and nutrients. One of the proteins that tells cells in the body to make new blood vessels is called VEGF. To start this process, VEGF attaches to a protein on the outside of the cancer cell called a VEGF receptor (VEGFR).

Ramucirumab (Cyramza)

Ramucirumab is a monoclonal antibody that binds to a VEGF receptor. This keeps VEGF from binding to cells and telling them to make more blood vessels. This can help slow or stop the growth of the cancer.

Ramucirumab is used to treat advanced stomach cancer, either by itself or along with chemo, most often after at least one chemo drug (or combination) stops working.

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

Side effects of ramucirumab

The most common side effects of this drug are high blood pressure, headache, and diarrhea.

Less common but possibly serious side effects can include blood clots, severe bleeding, holes forming in the stomach or intestines (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 CLDN18.2

Claudin 18.2 (CLDN18.2) is a protein that normally helps keep epithelial cells bound together. Epithelial cells are cells that are commonly found along the gastrointestinal tract. Stomach cancer cells sometimes have too much of this protein on their surface.

Zolbetuximab (Vyloy)

Zolbetuximab is a monoclonal antibody that targets CLDN18.2.  

If you have stomach 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 determine if you might be helped by this drug.

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

Side effects of zolbetuximab

Common side effects are nausea, vomiting, diarrhea, fatigue, decreased appetite, belly pain, weight loss, constipation, and decreased sensation in fingertips or toes (sensory neuropathy).

Less common but serious side effects can include low blood cell counts, which can increase a person’s risk of infections and bleeding; abnormal liver tests; and changes in electrolyte levels, such as sodium, phosphate, potassium, and magnesium.

Drugs that target TRK

In a small number of stomach 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), and repotrectinib (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.

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 test results, 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.

Many other drugs that target different parts of cancer cells are now being studied for use against stomach cancer as well.