Ripretinib for the treatment of advanced, imatinib‐resistant gastrointestinal stromal tumors

Abstract

Discovery of constitutive activation of KIT/PDGFRA tyrosine kinases in gastrointestinal stromal tumors (GISTs) leads to the development of the targeted drug imatinib. However, the inevitable development of imatinib resistance remains a major issue. Ripretinib is a novel targeted drug that inhibits the activities of a broad spectrum of drug‐resistant KIT/PDGFRA mutants. It was approved in 2020 and is currently recommended by major international guidelines as the fourth‐line and beyond therapy for advanced GISTs. Emerging evidence shows that ripretinib is superior to sunitinib as a second‐line treatment for KIT exon 11‐mutated GISTs due to its activity against highly heterogeneous frequently occurring secondary mutations. This review summarizes current data on the use of ripretinib to treat advanced imatinib‐resistant GISTs. We also propose future research directions to improve the targeted GIST treatment.