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Most advanced gastrointestinal stromal tumors (GISTs) start with cancer-causing cell changes, or mutations, in specific genes. Changes in proteins called KIT and PDGFRA most commonly cause this cancer, a sarcoma that forms in the digestive tract.

 The unique genes that make up GISTs help doctors diagnose them and target their treatment.

Treatment for GISTs

How your doctors treat GISTs depends on several things – the tumor’s size, its location, its genetic profile, and how quickly it is growing.

Standard treatment for GISTs includes:

  • Monitoring without treatment, also called “watchful waiting”
  • Surgery
  • Targeted drug therapies
  • Palliative (supportive) care


Some small GISTs do not grow or cause you any trouble. For these types of tumors, your doctor may advise watching the tumor closely but not treating it unless something changes. Some doctors disagree and think these small tumors should be removed.


If your GIST is confined to one area and can be safely operated on, your doctor will usually remove it with surgery. Doctors are careful to take out GISTs completely. They don’t respond well to standard cancer surgery follow-up treatments such as chemotherapy and radiation. If your tumor is small (fewer than 5 centimeters), then the surgery may be laparoscopic, which means a series of tiny cuts to your belly that allow doctors to insert surgical tools and remove the cancer.

Targeted drug therapies

If after surgery your cancer returns or has already spread at diagnosis – as in about 10%-25% of cases – then your treatment will likely consist of a class of drugs that target cancer-causing gene mutations. These drugs, called tyrosine kinase inhibitors (TKIs), work by blocking the cell changes that allow tumors to grow.

 TKIs come in the form of pills, which you’d normally take once a day. They are often given as long as they work and don’t cause serious side effects. TKIs used to treat GISTs can vary in how well they work against certain cancer-causing mutations. They can also stop working if you get more types of mutations.

Palliative care

Palliative, or supportive, care can be given at any time during your treatment if you have side effects or if your condition gets worse. Palliative care treats medical symptoms but can also help you manage the emotional and social sides of your cancer. This is also one of the rare times when radiation therapy is used with GIST, to ease symptoms such as bone pain.

Drugs Used to Treat Advanced GIST

Imatinib (Gleevec)

Most people with advanced GIST take imatinib at some point in their treatment. Imatinib is usually the first targeted therapy drug doctors use to treat GIST. Imatinib works by blocking the KIT and PDGFRA proteins from helping cancer cells grow and divide.

How it’s used:

  • If you had surgery, imatinib might be used to target cancer cells left around the edges of your removed tumor. Unless there’s a very low risk of your cancer returning, doctors usually recommend taking the drug for a year.
  • Imatinib also may work to shrink GISTs to a size where they can be removed by surgery.
  • If your advanced GISTs have spread too far from their original site, imatinib probably won’t cure your cancer. But it may shrink tumors or stop them from growing for several years.

Possible side effects of imatinib include mild stomach discomfort, diarrhea, muscle pain, rashes, and fluid retention. You can help ease stomach discomfort by taking the drug with food. Fluid retention mostly appears in the face or ankles and rarely appears in a more serious place such as the lungs or belly. Imatinib can also cause heart problems in some people.

Larger GISTs can be made up of lots of delicate blood vessels. If imatinib works too well and shrinks a tumor too quickly, it can lead to internal bleeding. Because of this possible side effect, your doctors will watch you very closely when you first start imatinib treatment.

Sunitinib (Sutent)

Doctors turn to sunitinib if imatinib stops working or you are no longer able to tolerate it. Like imatinib, it targets KIT/PDGFRA mutations but also targets some additional ones as well. Sunitinib works by shrinking the tumor or stopping its growth. You may feel really tired when you take this drug and have nausea, diarrhea, a sore mouth, or changes in skin and hair color. High blood pressure, bleeding risk, swelling, and heart and liver problems are its more serious side effects.

Regorafenib (Stivarga)

If both imatinib and sunitinib stop working, your doctor may try regorafenib. It also targets multiple proteins on the cancer cell. While it can slow or stop tumor growth, it’s unclear whether taking regorafenib helps people survive longer. 

Regorafenib carries a longer list of possible side effects, including:

  • Stomach pain or diarrhea
  • Loss of appetite and weight
  • Fatigue and weakness
  • Irritation in your mouth or throat
  • Fever

Unusual but more serious complications from regorafenib include infection, high blood pressure and heart ailments, bleeding, rashes, slow wound healing, and holes in the lining of the stomach or intestines as well as blisters, redness, or pain on the palms or the soles of the feet (hand-foot syndrome).

Avapritinib (Ayvakit)

In January 2020, another drug was approved as a first treatment for advanced GIST. It’s for people whose tumors can’t be removed surgically, have spread, and have a particular PDGFRA mutation that doesn’t respond well to other TKIs. Doctors believe avapritinib opened the door to the creation of even more treatments for advanced GIST with cancer-causing genetic mutations that don’t respond well to other TKIs. 

Avapritinib’s milder side effects are similar to those of other TKIs but may also include increased eye tearing, dizziness, and changes in hair color. More serious side effects may affect the brain and nervous system including drowsiness, confusion, forgetfulness, sleep issues, changes in mood or behavior, bleeding in the brain, and hallucinations.                                 

Ripretinib (Qinlock)

Ripretinib, approved in May 2020, is used to treat advanced GISTs if three or more TKIs – including imatinib – aren’t able to be used or no longer work. It also targets multiple cancer-causing cells and works by shrinking or slowing tumors. Its effect on survival is not yet known. Ripretinib has many of the same side effects as regorafenib but also can cause constipation, hair loss, and muscle pain. As with regorafenib, heart problems, high blood pressure, hand-foot syndrome, and slow wound healing are serious but rare side effects. So is an increased risk of skin cancer. 

Other Forms of Treatment

In addition to standard care, people with advanced GIST may be able to sign up for clinical trials testing new treatments. For some people, this is the best treatment option. Clinical trials can be available for people at any stage of their disease. Your doctor can tell you if there are any trials suitable for you, or you can search for them on the National Cancer Institute website or at

And remember: Get palliative care to help relieve troublesome symptoms of GIST and side effects and improve your quality of life while getting your treatment.

Show Sources

Photo Credit: Images


American Cancer Society: “If You Have a Gastrointestinal Stromal Tumor (GIST),” “Targeted Drug Therapy for Gastrointestinal Stromal Tumors,” “Typical Treatment Options for Gastrointestinal Stromal Tumors.”

National Cancer Institute: “Gastrointestinal Stromal Tumors Treatment (Adult) (PDQ) – Patient Version.”

Cancer: “An Updated Review of the Treatment Landscape for Advanced Gastrointestinal Stromal Tumors.”

National Organization for Rare Disorders (NORD): “Gastrointestinal Stromal Tumors.” “Important Safety Information.”