ABSTRACT
INTRODUCTION: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. Imatinib mesylate revolutionized the management of advanced/metastatic GIST, and remains the standard first-line therapy in this setting. Upon development of secondary resistance, sunitinib and regorafenib are used as subsequent treatments, although clinical benefit is often non-durable. Ripretinib is a type II kinase inhibitor targeting KIT and PDGFRA mutations and resistance through switching active I and inactive II forms. AREAS COVERED: This drug profile article provides an overview of the current state of the art treatment algorithm for advanced/metastatic GIST, focusing on the role of ripretinib in the fourth-line setting as defined by currently available clinical trials evidence. The mechanism of action, the safety profile, efficacy, and clinical application of ripretinib are presented. In addition, the Phase I study (NCT02571036) through which the optimal dose was established and the Phase III trials that assessed the efficacy and safety of ripretinib as fourth- (INVICTUS) and second-line treatment (INTRIGUE) are presented. EXPERT OPINION: Ripretinib is a safe and an effective therapy for the fourth-line setting in advanced/metastatic GIST. Future studies should evaluate combination schedules and the identification of markers predictive of benefit from ripretinib.
