Lancet oncol: Phase III Trial: The Efficacy and Safety of Ripretinib Single Drug for the Treatment of Late Gastroenteric Tumors

Resistance to approved KIT primary cancer genes, receptor tyrosine kinase (KIT) and platelet-source growth factor receptor (PDGFRA) inhibitors is a clinical challenge for patients with advanced gastrointestinal tumorsThe purpose of this study was to compare the efficacy and safety of ripretinib (a switchcontrol tyrosine kinase inhibitor that is active with a wide range of KIT and PDGFRA mutations) with a placebo in patients with advanced gastrointestinal interstitial tumors previously treatedThis study is a two-blind, randomized, placebo-controlled phase 3 trial in which patients with advanced gastrointestinal tumors over the age of 18 were recruited from 29 specialist hospitals in 12 countries, with at least imartinib, shonetinib, and regrafini treatment, with progression or intolerance to these treatmentsThe subjects were randomly divided into the ripretinib group (ripretinib 150 mg/day, oral) or the placebo group at 2:1From February 27, 2018 to November 16, 2018, 154 patients were assessed, and 129 patients were eventually included, and were randomly assigned to the ripretinib group (85) or the placebo group (44)As of May 31, 2019, the ripretinib group and the placebo group followed up with the median of 6.3 months (IQR 3.2-8.2) and 1.6 months (1.1-2.7), respectively, with 51 and 37 patients with no progression survival eventsIn the double-blind stage, the median progression-free survival period in the ripretinib group and the placebo group were 6.3 months and 1.0 months, respectivelyThe most common adverse events associated with emergency treatment in the Ripretinib group were elevated lipase (5%), hypertension (4%), fatigue (2%) and hypophosphate (2%), while in the placebo group, the most common were anemia (7%), fatigue (2%), diarrhea (2%), nachio (2%), dehydration (2%), hyperkalemia (2%), acute kidney damage (2%) and pulmonary edema (2%)In addition, the ripretinib group and the placebo group had 8 (9%) and 3 (7%) treated for severe adverse reactions, respectivelyOne treatment-related death in each of the two groups (patients in the placebo group died of infectious shock and pulmonary edema, and patients in the ripretinib group died from sleep ingreinib, the cause of death was unknown)Compared to placebo, ripretinib significantly improved the median progression less progressive survival in patients with advanced gastrointestinal tumors, and was safe within acceptable ranges