Ripretinib Research Articles

Effect and safety of ripretinib in the treatment of advanced gastrointestinal stromal tumor: A systematic review and meta-analysis.

Imatinib (IMA) has received approval as the primary treatment for gastrointestinal stromal tumors (GIST). Nonetheless, approximately half of the patients with advanced GIST show disease advancement following IMA treatment. Presently, the efficacy of secondary and tertiary medications in addressing various GIST secondary mutations is somewhat restricted. Consequently, there is a significant medical demand for the creation of kinase inhibitors that extensively block secondary drug-resistant mutations in advanced GIST. Ripretinib (RPT) is a new, switch-control tyrosine kinase inhibitors that can suppress different mutations of KIT and PDGFRA via a dual mechanism of action. To investigate the literature on RPT to assess an effective, safe, and successful treatment strategy against advanced GIST. The present systematic review and meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase, Cochrane, Web of Science and ClinicalTrials.gov databases were screened from January 1, 2003 to May 1, 2024. A total of 4 studies were included, with a total of 507 patients enrolled. The objective response rate (ORR) of the RPT-treated advanced GIST was 17% (95%CI: 0.11-0.27), while the disease control rate (DCR) was 66% (95%CI: 0.59-0.73). The overall occurrence of adverse events with varying degrees was 97% (95%CI: 0.93-1), whereas that of grade ≥ 3 adverse reactions was 42% (95%CI: 0.28-0.63). The sensitivity analysis revealed that omitting some studies did not yield statistically notable variances in the aggregate data regarding the ORR, DCR, and the occurrence of adverse events of grade 3 or higher. The publication bias was absent because no significant asymmetry was observed in Begg's funnel plot in all studies. RPT has favorable efficacy profiles in GIST patients, but the adverse reactions are obvious, and patient management needs to be strengthened to achieve better safety and tolerability.

Propylene carbonate as an ecofriendly solvent: Stability studies of Ripretinib in RPHPLC and sustainable evaluation using advanced tools

Ripretinib (RPB) is a U.S. Food and Drug Administration approved drug for the treatment of advanced gastrointestinal stromal tumour. According to literature search, there are no RP-HPLC methods developed for the recently approved drug RPB due to its terrible solubility. In this current study, Green Analytical Chemistry (GAC) was employed using the RP-HPLC technique to study the stability of RPB under different stress conditions. Two reported polymorphs of RPB were analysed using the mobile phase mixture of phosphate buffer, propylene carbonate and ethanol (50: 35: 15) on a 250 × 4.6 mm, i.d. 5 μm Inertsil ODS-2 C18 column, at a wavelength of 260 nm. In this study, method development for RPB quantification was accomplished within a linearity range of 1400–2600 ng/mL, yielding an R2 value of 0.9973. The method exhibited a LOD of 103 ng/mL and a LOQ of 312 ng/mL, demonstrating high sensitivity and accuracy. The utilization of assessment tools for evaluating greenness and whiteness offered valuable insights into the environmental impact and sustainability of the proposed methodology. The results substantiated its positive performance in terms of eco-friendliness, thereby emphasizing its alignment with seven sustainable development goals include 7 (Affordable and Clean Energy), 9 (Industry, Innovation, and Infrastructure), 12 (Responsible Consumption and Production), 13 (Climate Action), 14 (Life Below Water), 15 (Life on Land), 17 (Partnerships for the Goals). This further enhances the credibility and significance of the developed method in advancing the cause of a greener and more sustainable future.

Neuropsychiatric Adverse Drug Reactions with Tyrosine Kinase Inhibitors in Gastrointestinal Stromal Tumors: An Analysis from the European Spontaneous Adverse Event Reporting System

Tyrosine kinase inhibitors (TKIs) are widely used in gastrointestinal stromal tumors (GISTs). The aim of this study is to evaluate the reporting frequency of neuropsychiatric adverse drug reactions (ADRs) for TKIs through the analysis of European individual case safety reports (ICSRs). All ICSRs collected in EudraVigilance up to 31 December 2021 with one TKI having GISTs as an indication (imatinib (IM), sunitinib (SU), avapritinib (AVA), regorafenib (REG), and ripretinib (RIP)) were included. A disproportionality analysis was performed to assess the frequency of reporting for each TKI compared to all other TKIs. The number of analyzed ICSRs was 8512, of which 57.9% were related to IM. Neuropsychiatric ADRs were reported at least once in 1511 ICSRs (17.8%). A higher reporting probability of neuropsychiatric ADRs was shown for AVA. Most neuropsychiatric ADRs were known, except for a higher frequency of lumbar spinal cord and nerve root disorders (reporting odds ratio, ROR 4.46; confidence interval, CI 95% 1.58-12.54), olfactory nerve disorders (8.02; 2.44-26.33), and hallucinations (22.96; 8.45-62.36) for AVA. The analyses of European ICSRs largely confirmed the safety profiles of TKIs in GISTs, but some ADRs are worthy of discussion. Further studies are needed to increase the knowledge of the neuropsychiatric disorders of newly approved TKIs.