Targeted Therapy Drugs for Gastrointestinal Stromal Tumors

This drug is used to treat most people with GISTs. Tumors can be tested for certain changes in the KIT and PDGFRA genes before treatment, which can help tell how likely it is that imatinib will be helpful.

Many GISTs shrink when treated with imatinib. Some other tumors stop growing for a time. A small number of tumors are not helped by this treatment. In these cases, other TKI drugs might be tried.

Imatinib can be helpful in different situations.

Adjuvant therapy

Adjuvant therapy is treatment given after surgery. If a GIST has been removed completely by surgery, doctors often recommend taking imatinib afterward unless the risk of the cancer coming back is low.

Many doctors recommend at least 3 years of treatment with imatinib after surgery for patients who have a higher risk of their tumors returning based on the tumor’s size, location, and mitotic rate.

Neoadjuvant therapy

Neoadjuvant therapy is treatment given before surgery. For larger tumors that might be hard to remove, imatinib might be used first to try to shrink the tumor and make surgery easier. Imatinib is also given after surgery (adjuvant therapy) when used early on for a total of at least 3 years.

Advanced GISTs

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 might help slow the growth for some time, but higher doses can also have more side effects.

Possible side effects

Side effects of imatinib can include mild stomach upset, diarrhea, muscle pain, low energy, 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 around the eyes or in the ankles.

Rarely, it can cause more severe problems, such as fluid building up in the lungs or the abdomen. It can also affect the heart or thyroid function in some people.

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.

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. It might work better for people with “wild-type GIST,” or those that don’t have mutations in the KIT or PDGFRA genes.

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

Possible side effects

Common side effects include low energy, nausea, diarrhea, belly pain, low appetite, mouth irritation, thyroid problems, and skin and hair changes.

More serious side effects can include high blood pressure, increased risk of bleeding, swelling, heart problems, and serious liver problems.

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 other TKIs.

Possible side effects

Common side effects include swelling or fluid retention, low energy, nausea and vomiting, loss of appetite, diarrhea or constipation, increased tears in the eyes, hair 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

Regorafenib can be used to treat advanced 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.

Possible side effects

Common side effects include belly pain, diarrhea, feeling tired or weak, mouth or throat irritation, fever, loss of appetite, and weight loss.

Less common but more serious side effects can include infections, high blood pressure, heart problems, serious bleeding, trouble with wound healing, holes forming in the wall of the stomach or intestines, severe rashes, and hand-foot syndrome (redness, pain, or blistering of the palms of the hands and soles of the feet).

Ripretinib is typically used to treat advanced GISTs if other TKIs such as imatinib, sunitinib, and regorafenib are no longer helpful, or if a person can’t take these drugs for some reason. This drug targets many proteins, including KIT and PDGFRA.

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

Possible side effects

Common side effects include hair loss, nausea and vomiting, loss of appetite, diarrhea or constipation, feeling tired, and muscle or belly pain.

Less common but more serious side effects can include high blood pressure, an increased risk of new skin cancers, heart problems, trouble with wound healing, and hand-foot syndrome (redness, pain, or blistering of the palms of the hands and soles of the feet).

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

• Sorafenib (Nexavar)
• Nilotinib (Tasigna)
• Dasatinib (Sprycel)
• Pazopanib (Votrient)
• Cabozantinib (Cometriq)
• Ponatinib (Iclusig)