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
Martín-Broto, Javier (Hospital Universitario General de Villalba)
Valverde, Claudia (Vall d'Hebron Institut d'Oncologia)
Hindi, Nadia (Hospital Universitario General de Villalba)
Vincenzi, Bruno (University Campus Bio-Medico and Fondazione Policlinico Universitario Campus Bio-Medico (Roma, Itàlia))
Martínez-Trufero, Javier (Hospital Universitario Miguel Servet (Saragossa))
Grignani, Giovanni (Città della Salute e della Scienza Hospital (Turin, Itàlia))
Italiano, Antoine (Institute Bergonié (Burdeus, França))
Lavernia, Javier (Fundación Instituto Valenciano de Oncologia)
Vallejo, Ana (Hospital Regional Universitario de Málaga)
Tos, Paolo Dei (University of Padua. Department of Medicine)
Le Loarer, Francois (Pathology department, Institute Bergonié)
Gonzalez-Campora, Ricardo (Hospital Quironsalud (Córdoba, Andalusia))
Ramos, Rafael (Hospital Universitari Son Espases (Palma de Mallorca, Balears))
Hernández-Jover, Diana (Institut d'Investigació Biomèdica Sant Pau)
Gutiérrez, Antonio (Hospital Universitari Son Espases (Palma de Mallorca, Balears))
Serrano, Cesar (Vall d'Hebron Institut d'Oncologia)
Monteagudo, Maria (Centro Nacional de Investigaciones Oncológicas)
Letón, Rocio (Centro Nacional de Investigaciones Oncológicas)
Robledo, Mercedes (Centro Nacional de Investigaciones Oncológicas)
Moura, David S. (Hospital Universitario Fundación Jiménez Díaz)
Martin-Ruiz, Marta (Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz)
López-Guerrero, Jose A. (Fundación Instituto Valenciano de Oncologia (Madrid))
Cruz, Julia (Fundación Instituto Valenciano de Oncologia (Madrid))
Fernandez-Serra, Antonio (Fundación Instituto Valenciano de Oncologia)
Blay, Jean-Yves (Centre Léon Bérard (França))
Fumagalli, Elena (Istituto Nazionale dei Tumori (Milà, Itàlia))
Martínez-Marin, Virginia (Hospital Universitario La Paz (Madrid))
Universitat Autònoma de Barcelona

Data:	2023
Resum:	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.
Ajuts:	Instituto de Salud Carlos III CD20/00155 European Commission 825806
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Wild type GIST ; SDH: Regorafenib ; Biomarker ; Clinical trial
Publicat a:	Molecular cancer, Vol. 22 (august 2023) , ISSN 1476-4598

DOI: 10.1186/s12943-023-01832-9
PMID: 37559050

8 p, 1.0 MB

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