Immunotherapy Treatment for Advanced GIST Cancer

Immuno-oncology (or immunotherapy) and precision medicine are the newest developments in the treatment of advanced cancer.  Immuno-oncology helps to restore the body’s immune system and improves outcomes when administered alone or in combination with chemotherapy or when chemotherapy is not often given, as with GIST.

Immunotherapy is class of treatments that take advantage of a person’s own immune system to help kill cancer cells. There are currently several FDA-approved targeted therapy options for the treatment of GIST.

The targeted drugs used to treat GISTs are called tyrosine kinase inhibitors (TKIs).  TKIs target proteins that are tyrosine kinases, such as KIT and PDGFRA and are treatments that can be taken in a pill form, usually once a day.

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

Imatinib (Gleevec):  a mainstay 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.

Sunitinib (Sutent): 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.

Regorafenib (Stivarga): 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.

Ripretinib (Qinlock):  Ripretinib is 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 kinase proteins, including KIT and PDGFRA.

Avapritinib (Ayvakit): a 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. 

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)

 

The goal of immunotherapy is to help the immune system recognize and eliminate cancer cells by either activating the immune system directly, or by inhibiting mechanisms of suppression of the cancer.

In an attempt to improve the chance of cure, immunotherapies are being tested alone or in combination with chemotherapy in clinical trials.