Tyrosine Kinase Inhibitor (TKI) Therapy

TKIs work by inhibiting aberrantly functioning KIT or PDGFRA receptor tyrosine kinases and inducing rapid reduction in tumor growth. TKI therapy is indicated for patients with unresectable, borderline resectable, metastatic, or recurrent GISTs. It is also indicated as adjuvant therapy for patients with GISTs at high risk of recurrence.

The TKI imatinib mesylate is used as first-line therapy for most patients with KIT- and PDGFRA-variant GISTs.[14] For patients with GISTs characterized by a PDGFRA D842V variant, avapritinib is used as first-line therapy, given the high clinical benefit and imatinib-resistance in this subtype.[15] Other TKI agents approved for subsequent lines of therapy in patients with KIT/PDGFRA-variant GISTs include sunitinib, regorafenib, and ripretinib. Additional TKI agents that are occasionally given include nilotinib, sorafenib, and pazopanib.

Imatinib is not typically given to patients with KIT/PDGFRA wild-type GISTs (i.e., SDH-deficient or neurofibromatosis type 1 [NF1]-related GISTs) because of high rates of resistance. Other TKIs (i.e., sunitinib or regorafenib) may have some activity, but most patients are recommended to consider enrolling in clinical trials, if eligible.

For more information on the efficacy, safety, and management of toxicity of imatinib, or additional agents in the setting of imatinib resistance or intolerance, see the sections on Treatment of Resectable Primary GISTs, Treatment of Unresectable Primary GISTs, and Treatment of Metastatic or Recurrent GISTs.