Targeted Drug Therapy for Gastrointestinal Stromal Tumors

Some drugs can target certain proteins in gastrointestinal stromal tumor (GIST) cells that help them divide and grow. These targeted drugs (sometimes called precision drugs) are often very helpful in treating GISTs. They work differently from standard chemotherapy (chemo) drugs, which are usually not helpful.

The targeted drugs used to treat GISTs are called tyrosine kinase inhibitors (TKIs), because they target proteins that are tyrosine kinases, such as KIT and PDGFRA.

All of these targeted drugs are pills, taken once a day.

Imatinib (Gleevec)

This drug is used to treat most people with GISTs at some point. Tumors can be tested for certain mutations in the KIT and PDGFRA genes before treatment, which can help tell how likely it is that imatinib will be helpful. This drug targets both the KIT and PDGFRA proteins, blocking their ability to help tumor cells grow and divide. In most GISTs, the cells have too much of one of these proteins.

Most GISTs shrink when treated with imatinib. Some other tumors at least stop growing for a time. A small number of tumors are not helped by this treatment.

Imatinib can be helpful in different situations:

  • If a GIST has been removed completely by surgery, doctors typically recommend taking imatinib for at least a year afterward (unless the risk of the cancer coming back is low). This is known as adjuvant therapy. Many doctors now recommend at least 3 years of imatinib after surgery for patients who have a higher risk of their tumors returning (based on the tumor’s size, location, and mitotic rate).
  • For larger tumors that may be hard to remove, imatinib may be used first to try to shrink the tumor and make surgery easier. This is known as neoadjuvant therapy. Imatinib is often given again after surgery as well, typically for at least 2 years.
  • Imatinib is usually the treatment of choice for advanced GISTs that have spread too far to be removed by surgery. While it's unlikely to cure these tumors, it can often shrink or slow their growth for several years, helping people live longer and feel better. If the drug stops working and the tumor starts growing again, raising the dose of imatinib may help slow the growth for some time, but higher doses can also have more side effects.

Side effects of imatinib can include mild stomach upset, diarrhea, muscle pain, and skin rashes. The stomach upset is lessened if the drug is taken with food. Imatinib can also make people retain fluid. Often this causes some swelling in the face (around the eyes) or in the ankles. The drug rarely can cause more severe problems, such as fluid building up in the lungs or in the abdomen. It can also affect heart function in some people.

One other concern when using this drug to treat large GISTs is that these tumors often have a lot of fragile blood vessels. If imatinib causes the tumor to shrink quickly, it could lead to internal bleeding. For this reason, doctors watch patients carefully when they first start taking this drug.

Sunitinib (Sutent)

This drug can be useful in treating GISTs if imatinib is no longer working or if a person can’t take imatinib for some reason.

Sunitinib targets the KIT and PDGFRA proteins, as well as several other proteins that imatinib does not target.

Sunitinib helps some people, usually by shrinking or slowing the growth of the tumor. This may help some people live longer.

Common side effects of sunitinib include fatigue, nausea, diarrhea, mouth irritation, and skin and hair color changes. More serious side effects can include high blood pressure, increased risk of bleeding, swelling, heart problems, and serious liver problems.

Regorafenib (Stivarga)

Regorafenib can be used to treat GISTs if imatinib and sunitinib stop working, or if a person can’t take these drugs for some reason. This drug targets many proteins, including KIT and PDGFRA.

Regorafenib can slow tumor growth and even shrink some tumors, although it’s not clear if it can help people live longer.

Common side effects of regorafenib include diarrhea, fatigue, high blood pressure, mouth irritation, hair loss, loss of appetite, and problems with redness, pain, or even blistering of the palms of the hands and soles of the feet (called hand-foot syndrome).

Avapritinib (Ayvakit)

This is another TKI that targets PDGFRA and KIT, as well as several other proteins.

Avapritinib is used mainly to treat advanced GISTs whose cells have a change in the PDGFRA gene known as an exon 18 mutation. These cancers typically don’t respond well to treatment with the TKIs above. 

Common side effects of avapritinib can include swelling or fluid retention, fatigue, nausea and vomiting, loss of appetite, diarrhea or constipation, increased tears in the eyes, hair color changes, belly pain, rash, and dizziness. 

More serious side effects can include bleeding in the brain, as well as central nervous system (CNS) effects, such as:

  • Forgetfulness
  • Confusion
  • Trouble thinking
  • Drowsiness
  • Trouble sleeping
  • Hallucinations
  • Changes in mood or behavior

Other tyrosine kinase inhibitors

Several other TKIs are now being studied for use against GISTs as well. While there is limited evidence on how useful they are, some of the TKIs that might be options if those listed above are no longer working include:

  • Sorafenib (Nexavar)
  • Nilotinib (Tasigna)
  • Dasatinib (Sprycel)
  • Pazopanib (Votrient)

Because it’s not exactly clear how well these and other TKIs work against GISTs, taking part in a clinical trial studying them might be a good option.

More information about these types of drugs and the side effects they can cause can be found in Targeted Cancer Therapy.

The American Cancer Society medical and editorial content team

Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

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Morgan J. Tyrosine kinase inhibitor therapy for advanced gastrointestinal stromal tumors. UpToDate. 2019. Accessed at on October 21, 2019.

Morgan J, Raut CP. Adjuvant and neoadjuvant imatinib for gastrointestinal stromal tumors. UpToDate. 2019. Accessed at on October 21, 2019.

National Cancer Institute. Physician Data Query (PDQ). Gastrointestinal Stromal Tumors Treatment. 2018. Accessed at on October 21, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Soft Tissue Sarcoma. V.4.2019. Accessed at on October 21, 2019.

Last Medical Review: December 1, 2019 Last Revised: January 9, 2020

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