Sistema de Salut de Catalunya
Institut Català de la Salut
[George S] Dana-Farber Cancer Institute, Boston, MA, USA. [Blay JY] Centre Léon Bérard, Lyon, France. [Chi P] Memorial Sloan Kettering Cancer Center, New York, NY, USA. Weill Cornell Medicine, New York, NY, USA. [Jones RL] Sarcoma Unit, The Royal Marsden NHS Foundation Trust & Institute of Cancer Research, London, UK. [Serrano C] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Somaiah N] The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Vall d'Hebron Barcelona Hospital Campus
2024-10-25T09:32:34Z
2024-10-25T09:32:34Z
2024
KIT mutations; Gastrointestinal stromal tumor; Targeted therapy
Mutaciones KIT; Tumor del estroma gastrointestinal; Terapia dirigida
Mutacions KIT; Tumor de l'estroma gastrointestinal; Teràpia dirigida
Somatic KIT activating mutations drive most gastrointestinal stromal tumors (GISTs). Disease progression eventually develops with first-line imatinib, commonly due to KIT secondary mutations, and different kinase inhibitors have various levels of treatment efficacy dependent on specific acquired resistance mutations. Ripretinib is a broad-spectrum switch-control KIT/PDGFRA tyrosine kinase inhibitor for patients with advanced GIST who received prior treatment with three or more kinase inhibitors, including imatinib. Exploratory baseline circulating tumor DNA analysis from the second-line INTRIGUE trial determined that patients with advanced GIST previously treated with imatinib harboring primary KIT exon 11 mutations and secondary resistance mutations restricted to KIT exons 17/18 had greater clinical benefit with ripretinib versus sunitinib. We describe the rationale and design of INSIGHT (NCT05734105), an ongoing Phase III open-label study of ripretinib versus sunitinib in patients with advanced GIST previously treated with imatinib exclusively harboring KIT exon 11 + 17/18 mutations detected by circulating tumor DNA.
This study is sponsored by Deciphera Pharmaceuticals, LLC.
Article
Published version
English
Anomalies cromosòmiques; Tracte gastrointestinal - Càncer - Tractament; Proteïnes quinases - Inhibidors - Ús terapèutic; PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation; DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Connective and Soft Tissue::Neoplasms, Connective Tissue::Gastrointestinal Stromal Tumors; Other subheadings::Other subheadings::Other subheadings::/drug therapy; CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protein Kinase Inhibitors; Other subheadings::Other subheadings::/therapeutic use; FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación; ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias de tejido conjuntivo y de tejidos blandos::neoplasias de tejido conjuntivo::tumores del estroma gastrointestinal; Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia; COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::inhibidores de proteínas cinasas; Otros calificadores::Otros calificadores::/uso terapéutico
Taylor & Francis
Future Oncology;20(27)
https://doi.org/10.1080/14796694.2024.2376521
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
