Gastrointestinal stromal tumors (GISTs) are the most common gastrointestinal mesenchymal tumors. Treatment of metastatic GISTs is determined by the molecular subtype of the tumor. The use of tyrosine kinase inhibitors, in particular imatinib, which is used as the standard first line treatment for metastatic tumors has been a revolution in the treatment of GIST. Despite the high efficacy of the drug, most patients develop resistance to the treatment, usually after 2–3 years. In the second and third lines of treatment, such drugs as sunitinib and regorafenib are used, respectively. In 2020, the FDA approved ripretinib as a fourth-line treatment, and in the presence of a mutation in the 18th exon of the PDGFRA gene; avapritinib began to be used from the same year. This review article describes standards and therapeutic approaches for the treatment of metastatic GISTs.

Keywords: ripretinib, avapritinib, regorafenib, tyrosine kinase inhibitors, imatinib, gastrointestinal stromal tumors, sunitinib