• Metastatic GIST is a type of cancer that starts in the gastrointestinal (GI) tract and spreads to distant tissues or organs.
  • Traditional chemotherapy and radiation aren’t usually effective in treating GISTs.
  • New targeted biologic therapies provide more promising treatment options for people with advanced GIST.

Gastrointestinal stroma tumors (GISTs) start in cells in the wall of the GI tract. Most GISTs grow slowly, but some spread quickly.

Like all cancers, GISTs can spread to distant parts of the body. This process is known as metastasis.

Here’s what you need to know about metastatic GIST, how it’s typically treated, and how newer therapies offer a more personalized and possibly effective approach to treatment.

GISTs are part of a group of cancers called sarcomas. The stomach is the most common place for GISTs to develop, followed by the small intestine. But they can develop anywhere along the GI tract, from the esophagus to the rectum.

Metastatic GIST means that cancer has spread to distant tissues or organs outside of the GI tract.

Ways cancer can spread

Cancer can spread in several ways, including through:

  • Tissues. As the primary tumor grows, it invades nearby tissues and organs.
  • Lymph nodes. Cancer cells can break away from the primary tumor and enter nearby lymph nodes. From there, they can move throughout the body.
  • Blood vessels. If cancer cells enter a blood vessel, they can move through the bloodstream to just about any part of the body.

Eventually, cancer cells start forming new tumors.

Some types of GISTs are more likely to spread than others, depending on the location and size of the primary tumor.

Another key factor is how fast cancer cells are dividing. This is called the mitotic rate.

A high mitotic rate means the cancer can spread quickly and may be more likely to recur even after treatment.

Treating metastatic GIST is more challenging than treating localized GIST that hasn’t spread.

Where can it spread?

A cancer’s spread is categorized as either:

  • Regional. This is when the cancer has grown into nearby organs or is found in nearby lymph nodes.
  • Distant. The cancer has spread to other areas of the body, such as the liver.

Cancer can spread anywhere. GISTs tend to spread first within the abdominal cavity, such as the liver or the lining of the abdomen.

Less often, GIST spreads to the lungs or bones. It rarely spreads to lymph nodes.

Survival rates are directly related to the staging of the disease.

The 5-year relative survival rate for a GIST that is localized (has not yet spread) is up to 93 percent, according to the American Cancer Society. A GIST that has metastasized locally has a survival rate of 80 percent, and those that have metastasized distally (or spread to other areas of the body) have a survival rate of 55 percent.

This is just a statistic based on people diagnosed with GIST between 2010 and 2016. Newer therapies have been approved since then that may affect the outlook for GISTs today.

Other factors that affect survival rates include:

  • a person’s age
  • the tumor’s location
  • the tumor’s size
  • the tumor’s mitotic rate
  • the tumor’s genotype and whether it has specific kinase mutations
  • whether the tumor ruptures, either spontaneously or during surgery

Your doctor can evaluate these factors to give you a better idea what to expect in your specific case.

Traditional chemotherapy isn’t an effective treatment for metastatic GIST. Surgery may be an option but depends on:

  • the number of tumors
  • where they’re located
  • tumor size
  • whether they can safely be removed

There are now five tyrosine kinase inhibitors (TKIs) approved for treatment of metastatic GIST. These oral medications work by targeting specific changes in cancer cells that help them grow and spread.

Because TKIs target cancer cells, they cause less harm to healthy cells than traditional therapies. Targeted treatments can be used before or after surgery.

Imatinib mesylate

Imatinib mesylate (Gleevec) has been the first-line therapy for metastatic GIST since 2000.

It’s a selective inhibitor of KIT and PDGFRA. These are two proteins that help cells grow. Most GIST tumors are positive for KIT.

Imatinib can often help shrink or stabilize tumors within a few months. Some tumors can then be surgically removed. Those that remain may start to grow again within a few years.

Sunitinib

If there’s no response to imatinib, or you can’t tolerate the side effects, your doctor can switch you to sunitinib (Sutent). This drug targets a variety of proteins, including KIT and PDGFRA proteins.

Regorafenib

After trying imatinib and sunitinib, the next step is regorafenib (Stivarga). It also targets KIT, PDGFRA, and other proteins.

Avapritinib

In January 2020, the Food and Drug Administration (FDA) approved avapritinib (Ayvakyt) for metastatic GIST that can’t be removed surgically.

It’s for cancers with a specific exon 18 mutation in the PDGFRA gene. This particular mutation doesn’t typically respond well to imatinib, sunitinib, or regorafenib.

Ripretinib

The newest targeted therapy for advanced GIST is ripretinib (Qinlock). Approved by the FDA in May 2020, ripretinib is for GISTs that aren’t adequately treated with imatinib, sunitinib, or regorafenib.

A double-blind, randomized, phase 3 study from 2020 compared ripretinib to a placebo. Ripretinib was found to significantly improve median progression-free survival rates.

Supportive care

Supportive care focuses on managing the symptoms of cancer and the side effects of treatment, with a goal of improving quality of life.

Treatments can include:

  • pain medication
  • radiation therapy
  • psychological and spiritual support

Cancer treatments are advancing all the time. Clinical trials are research studies that assess the safety and effectiveness of new treatments. Some also test new combinations or timing of already approved treatments.

In a clinical trial, you may gain access to experimental treatments you can’t get anywhere else.

Many other TKIs are being studied for their potential to treat GISTs. Some of these are:

  • crenolanib
  • dasatinib
  • masitinib
  • motesanib
  • nilotinib
  • pazopanib
  • sorafenib

More research is needed to see if any of these drugs can successfully treat metastatic GISTs. If you’re interested in joining a trial, your oncologist can help you determine if one is right for you.

Metastatic GIST is a type of advanced GI cancer.

The past two decades have brought significant changes in how these cancers are treated. Within the past few years, newer biologic therapies have provided more options and hope for people with metastatic GIST.

Talk with your doctor about these targeted therapies and how they might help you.