Monitoring the plasma concentration of ripretinib and its metabolites in Chinese patients with gastrointestinal stromal tumors in a real‐life setting

Background Although therapeutic drug monitoring is crucial for the comprehensive management of gastrointestinal stromal tumors (GISTs), the relationship between plasma concentration of ripretinib and its therapeutic efficacy is unknown. This study aimed to explore the relationship between ripretinib plasma trough concentration (R‐C trough ) and clinical efficacy and between ripretinib concentration and the incidence of adverse reactions among Chinese patients with advanced GIST. Methods The authors analyzed patients with GIST treated continuously for ≥1 month with a consistent daily dose ripretinib in a real‐life setting. Peripheral venous blood samples were collected 24 h after the previous dose to measure R‐C trough and 4 h after the current dose to identify the maximum concentration (R‐C 4 ). The plasma concentrations of ripretinib and its metabolites were quantified using liquid chromatography‐tandem mass spectrometry. Results Between June 2021 and October 2024, 102 patients receiving ripretinib were evaluated. Ripretinib treatment resulted in higher mean R‐C trough values in the nonprogression group than in the progression group ( p < .05). Patients exhibiting an R‐C trough above the threshold (R‐C min , 475 ng/mL) demonstrated a significant improvement in median progression‐free survival from 12.8 to 22.6 months ( p < .05). A correlation was observed between ripretinib blood concentration and the occurrence of alopecia, fatigue, hand‐foot syndrome, and rashes ( p < .05). Moreover, variability in blood–drug concentrations was observed among patients with different KIT genotypes. Conclusions Ripretinib and its metabolites maintained consistent plasma concentrations in Chinese patients with advanced GIST. Furthermore, a trough ripretinib concentration >475 ng/mL was associated with extended survival.