Targeted Drug Therapy for Stomach 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 (chemo) drugs. They sometimes work when standard chemo drugs don’t, and they often have different side effects.

Targeted drugs 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 of a growth-promoting protein called HER2 on their surface. Cancers with increased levels of HER2 are called HER2-positive. Drugs that target the HER2 protein can often be helpful in treating these cancers.

Trastuzumab (Herceptin, others)

Trastuzumab is a monoclonal antibody, a man-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 just chemo alone.

This drug only works 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 is infused into a vein (through an IV line or central venous catheter). For stomach cancer, it is typically given once every 2 or 3 weeks along with chemo.

Herceptin was the original brand name for trastuzumab, but several similar versions (called biosimilars) are now available as well, including Ogivri, Herzuma, Ontruzant, Trazimera, and Kanjinti.

Side effects of trastuzumab

The side effects of trastuzumab tend to be relatively mild. They can include fever and chills, weakness, nausea, vomiting, cough, diarrhea, and headache. These side effects occur less often after the first dose.

This drug can also rarely 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 signal 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). For stomach cancer, it is typically given once 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 of this drug 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 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 VEGF

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. The VEGF protein does this by attaching to cell surface proteins called VEGF receptors.

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 some cancers.

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

This drug is given as infusion into a vein (IV), typically once every 2 weeks. It can be given by itself or along with chemo.

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.

TRK inhibitors

A very small number of stomach cancers 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) and entrectinib (Rozlytrek) are drugs that target the TRK proteins. 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, 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 tests, heart problems, and confusion.

Drug that target CLDN18.2

Claudin 18.2 (CLDN18.2) is a protein that plays an important role in keeping healthy epithelial cells bound together. Epithelial cells are cells that are commonly found along the gastrointestinal tract.  When an epithelial cell turns into a cancer cell, however, CLDN18.2 may move to the surface of the cancer cell. As a result, CLDN18.2 can serve as a target for therapy.

Zolbetuximab (Vyloy)

Zolbetuximab is a monoclonal antibody  that targets CLDN18.2.  It is used to treat advanced stomach cancer that is HER2-negative and found to express high amounts of CLDN18.2 on their cell surface. For this type of stomach cancer, zolbetuximab can be given with chemo as the initial therapy.
 

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, stomach pain, weight loss, constipation, and decreased sensation in fingertips/toes (also called 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.

Other targeted drugs

Other targeted therapy drugs are now being tested against stomach cancer. Some of these target the HER2 protein, while others have different targets. Some of these drugs are discussed in more detail in What’s New in Stomach Cancer Research?