Abstract 97P
Background
The intrapatient escalation of ripretinib to 150 mg twice daily is advised following the failure of standard-dose therapy (150 mg once daily), suggesting a potential relationship between plasma concentrations of ripretinib and its efficacy. This study aims to explore the relationship between the plasma trough concentration (Cmin) of ripretinib and its clinical efficacy, as well as the association between the maximum concentration (Cmax) and the incidence of adverse events among Chinese patients with advanced GIST.
Methods
We retrospectively analyzed the patients with GIST who received a continuous fixed dose of Ripretinib for ≥1 month. Peripheral venous blood samples were collected at 24 hours after the previous dose to measure Cmin, and four hours after the current dose to identify Cmax. The plasma concentration of ripretinib and its metabolite (DP-5439) were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Machine learning KNN and Grid Search CV algorithms were utilized to determine the optimal threshold for Cmin.
Results
Between June 2021 and June 2024, a total of 83 patients who received ripretinib were investigated. Ripretinib and DP-5439 exhibited good consistency in plasm concentrations (P<0.05). Patients exhibiting a Cmin above the threshold (450 ng/mL) demonstrated a significant improvement in prognosis, with mPFS extending from 13.3 to 18 months (P<0.05). Both ripretinib and DP-5439 exhibited higher mean Cmin values in the non-progression group compared with the progression group, but the difference was not significant. And a correlation was found between the Cmax of ripretinib and the occurrence of asthenia (P<0.05). Moreover, variability in blood drug concentrations was also noted among patients with different KIT genotypes. Specifically, patients harboring KIT 9 or KIT 13 mutations exhibited lower drug concentrations than those with KIT 11 or KIT 17 mutations, although the difference was not significant.
Conclusions
The concentration of ripretinib significantly influences duration of tumor control treatment in GIST patients with a Cmin threshold of 450 ng/ml associated with prolonged PFS in real-life setting.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.