Targeted Therapy for Small Intestine Cancer (Adenocarcinoma)

Targeted 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.

When is targeted therapy used?

Targeted drugs work differently from chemotherapy (chemo) drugs. They sometimes work when chemo drugs don’t, and they often have different side effects. They can be used either along with chemo, by themselves, or in combination with another targeted therapy drug.

Like chemotherapy, these drugs enter the bloodstream and reach almost all areas of the body, which makes them useful against cancers that have spread to distant parts of the body.

Several types of targeted drugs might be used to treat small intestine cancer.

Drugs that target blood vessel formation (VEGF)

Vascular endothelial growth factor (VEGF) is a protein that helps tumors form new blood vessels (a process called angiogenesis) to get the nutrients they need to grow. Bevacizumab (Avastin) is a drug that stops VEGF from working and can be used to treat some small intestine cancers.

It is given as an infusion into your vein (IV) every 2 or 3 weeks, usually along with chemotherapy.

Possible side effects

Common side effects include:

• High blood pressure
• Protein in the urine
• Bleeding (from the nose or rectum)
• Headaches
• Taste changes
• Skin changes

Rare but possibly serious side effects include blood clots, severe bleeding, holes forming in the colon (called perforations), heart problems, kidney problems, and slow wound healing.

Another rare but serious side effect is an allergic reaction during the infusion, which could cause problems with breathing and low blood pressure.

Drugs that target cells with BRAF gene changes

A small portion of intestinal cancers have changes (mutations) in the BRAF gene. Cancer cells with these changes make an abnormal BRAF protein that helps them grow. Some drugs target this protein.

If you have small intestine cancer that has spread, your cancer will likely be tested to see whether the cells have a BRAF gene change known as BRAF V600E, which can cause the cell to make an abnormal BRAF protein.

Dabrafenib (Tafinlar) is a BRAF inhibitor, a drug that attacks the abnormal BRAF protein. This drug is given with trametinib (Mekinist), a MEK inhibitor.

This drug is taken as capsules, once a day.

Possible side effects

Common side effects of dabrafenib, in combination with trametinib, can include fever, fatigue, nausea, and rash.

Drugs that target cells with HER2 changes

In a small percentage of people with small intestine 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 or HER2-amplified. Drugs that target the HER2 protein, such as fam-trastuzumab deruxtecan (Enhertu, T-DXd), can often be helpful in treating these cancers.

Possible side effects

The side effects of HER2-targeted drugs tend to be mild overall, but some can be serious, and different drugs can have different possible side effects. Ask your cancer care team what you can expect.

Some of these drugs can cause heart damage during or after treatment, which might lead to congestive heart failure. Because of this, your doctor will likely check your heart function (with an echocardiogram or a MUGA scan) before treatment, and regularly while you are getting any of these drugs. Let your care team know if you develop symptoms such as shortness of breath, a fast heartbeat, leg swelling, or severe fatigue.

Some of these drugs can cause severe diarrhea, so it’s very important to let your care team know about any changes in bowel habits as soon as they happen.

Fam-trastuzumab deruxtecan can cause lung disease in some people, which might even be life-threatening. It’s very important to let your care team know right away if you’re having symptoms such as coughing, wheezing, trouble breathing, or fever.

Drugs that target cells with NTRK gene changes

A very small number of colorectal 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), entrectinib (Rozlytrek), and repotrectinib (Augtyro) 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 or an oral solution, once or twice daily.

Possible side effects

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, increased risk for fractures, heart problems, vision changes, and confusion.

Drugs that target cells with RET gene changes

A very small number of small intestine cancers have changes in one of the RET genes. This causes them to make abnormal RET proteins, which can lead to abnormal cell growth and cancer.

Selpercatinib (Retevmo) is a drug that targets the RET protein. It can be used to treat advanced cancers with RET gene changes that are still growing despite other treatments.

This drug is taken as a capsule twice daily.

Possible side effects

Common side effects of these drugs can include a decrease in white blood cell count and calcium, changes in liver function tests, high blood pressure, fatigue, changes in kidney function, and increased cholesterol.

Less common but serious side effects can include abnormal heart function (QTc interval prolongation, which is a change in the heart’s electrical rhythm), bleeding, allergic reaction, and inability to heal from a wound.

Drugs that target cells with KRAS gene changes

A very small number of small intestine cancers have the KRAS G12C gene mutation. This causes them to make abnormal KRAS proteins, which can lead to continued cell growth and cancer.

Adagrasib (Krazati) and sotorasib (Lumakras) are drugs that target the KRAS proteins.

These drugs are taken as tablets, once or twice daily.

Possible side effects

Common side effects of these drugs can include nausea, vomiting, diarrhea, muscle and joint pain, fatigue, decreased appetite, and changes in liver and kidney function.

Less common but serious side effects can include effects on the heart (QTc interval prolongation, which is a change in the heart’s electrical rhythm), liver, and lungs (interstitial lung disease).