Ripretinib in the treatment of patients with advanced gastrointestinal stromal tumors (GIST)

Abstract

Gastrointestinal stromal tumors (GISTs) are relatively rare in the population (0.4 to 2 cases per 100 000 per year) and account for approximately 1–2% of gastrointestinal cancers. According to the latest 2020 World Health Organization (WHO) classification of sarcomas, all GISTs are malignant, regardless of their size or mitotic index. In the systemic treatment of GIST, KIT tyrosine kinase receptor and platelet-derived growth factor receptor (PDGFRA) inhibitors, such as imatinib, sunitinib, or regorafenib, are used. The effectiveness of imatinib is significantly reduced in the case of secondary mutations in the KIT gene. The latest drug from the group of KIT inhibitors, ripretinib, was the first to show efficacy against most mutations associated with resistance, as well as in wild-type GIST, in which mutations in KIT and PDGFRA are not found. Analysis of the INVICTUS study showed a beneficial effect of ripretinib at the recommended dose of 150 mg/day on progression-free survival (PFS) in patients with advanced or metastatic GIST previously treated with at least three other inhibitors. However, the preliminary results of the phase III INTRIGUE study did not show an improvement in PFS in patients receiving ripretinib compared to sunitinib in the second-line therapy of GIST patients. Ripretinib has a favorable and acceptable safety profile and is recommended for treating patients with advanced GIST in the fourth line of treatment. In this article, we summarize the most essential data on the efficacy and safety of ripretinib in treating GIST patients and the recommendations for its use.