2026-04-17T06:06:18Zhttps://recercat.cat/oai/request

oai:recercat.cat:2072/4752722025-10-17T16:17:46Zcom_2072_98col_2072_378192

00925njm 22002777a 4500 dc Martín-Broto, Javier author Valverde, Claudia author Hindi, Nadia author Vincenzi, Bruno author Martínez-Trufero, Javier author Grignani, Giovanni author Italiano, Antoine author Lavernia, Javier author Vallejo, Ana author Tos, Paolo Dei author Le Loarer, Francois author Gonzalez-Campora, Ricardo author Ramos, Rafael author Hernández-Jover, Diana author Gutiérrez, Antonio author Serrano, Cesar author Monteagudo, Maria author Letón, Rocio author Robledo, Mercedes author Moura, David S. author Martin-Ruiz, Marta author López-Guerrero, Jose A. author Cruz, Julia author Fernandez-Serra, Antonio author Blay, Jean-Yves author Fumagalli, Elena author Martínez-Marin, Virginia author Universitat Autònoma de Barcelona author 2023 Approximately 15% of adult GIST patients harbor tumors that are wild-type for KIT and PDGFRα genes (KP-wtGIST). These tumors usually have SDH deficiencies, exhibit a more indolent behavior and are resistant to imatinib. Underlying oncogenic mechanisms in KP-wtGIST include overexpression of HIF1α high IGFR signaling through the MAPK pathway or BRAF activating mutation, among others. As regorafenib inhibits these signaling pathways, it was hypothesized that it could be more active as upfront therapy in advanced KP-wtGIST. Adult patients with advanced KP-wtGIST after central confirmation by NGS, naïve of systemic treatment for advanced disease, were included in this international phase II trial. Eligible patients received regorafenib 160 mg per day for 21 days every 28 days. The primary endpoint was disease control rate (DCR), according to RECIST 1.1 at 12 weeks by central radiological assessment. From May 2016 to October 2020, 30 patients were identified as KP-wtGIST by Sanger sequencing and 16 were confirmed by central molecular screening with NGS. Finally, 15 were enrolled and received regorafenib. The study was prematurely closed due to the low accrual worsened by COVID outbreak. The DCR at 12 weeks was 86.7% by central assessment. A subset of 60% experienced some tumor shrinkage, with partial responses and stabilization observed in 13% and 87% respectively, by central assessment. SDH-deficient GIST showed better clinical outcome than other KP-wtGIST. Regorafenib activity in KP-wtGIST compares favorably with other tyrosine kinase inhibitors, especially in the SDH-deficient GIST subset and it should be taken into consideration as upfront therapy of advanced KP-wtGIST. ClinicalTrials.gov Identifier: NCT02638766. The online version contains supplementary material available at 10.1186/s12943-023-01832-9. Wild type GIST SDH: Regorafenib Biomarker Clinical trial REGISTRI : Regorafenib in first-line of KIT/PDGFRA wild type metastatic GIST: a collaborative Spanish (GEIS), Italian (ISG) and French Sarcoma Group (FSG) phase II trial