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

The discovery of the constitutive activation of KIT/PDGFRA tyrosine kinases in gastrointestinal stromal tumors (GISTs) led 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 activity of a broad spectrum of drug-resistant KIT/PDGFRA mutants. It was approved in 2020 and is currently recommended in major international guidelines as fourth-line and beyond therapy for advanced GISTs. Emerging evidence shows that ripretinib is superior to sunitinib as 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 precision of targeted GIST treatment. This article is protected by copyright. All rights reserved.