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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.

التفاصيل البيبلوغرافية
العنوان: 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.
المؤلفون: Martin-Broto J; Health Research Institute-Fundación Jiménez Díaz University Hospital, Universidad Autonoma de Madrid (IIS-FJD, UAM), 28040, Madrid, Spain. jmartin@atbsarc.org.; Medical Oncology Department, Fundación Jimenez Diaz University Hospital, Av. de los Reyes Católicos, 2, 28040, Madrid, Spain. jmartin@atbsarc.org.; General de Villalba University Hospital, 28400, Madrid, Spain. jmartin@atbsarc.org., Valverde C; Medical Oncology department, Vall d'Hebron University Hospital, 08035, Barcelona, Spain., Hindi N; Health Research Institute-Fundación Jiménez Díaz University Hospital, Universidad Autonoma de Madrid (IIS-FJD, UAM), 28040, Madrid, Spain.; Medical Oncology Department, Fundación Jimenez Diaz University Hospital, Av. de los Reyes Católicos, 2, 28040, Madrid, Spain.; General de Villalba University Hospital, 28400, Madrid, Spain., Vincenzi B; Medical Oncology, University Campus Bio-Medico and Fondazione Policlinico Universitario Campus Bio-Medico, 00128, Rome, Italy., Martinez-Trufero J; Medical Oncology Department, University Hospital Miguel Servet, 50009, Zaragoza, Spain., Grignani G; Medical Oncology Unit, Città della Salute e della Scienza Hospital, 10126, Turin, Italy., Italiano A; Medical Oncology department, Institute Bergonié, 33076, Bordeaux, France., Lavernia J; Medical Oncology department, Fundación Instituto Valenciano de Oncologia, 46009, Valencia, Spain., Vallejo A; Pathology department, Hospital Regional Universitario de Malaga, 29010, Malaga, Spain., Tos PD; Department of Medicine, School of Medicine, University of Padua, 35122, Padua, Italy., Le Loarer F; Pathology department, Institute Bergonié, 33076, Bordeaux, France., Gonzalez-Campora R; Pathology department, Hospital Quironsalud, 14004, Cordoba, Cordoba, Spain., Ramos R; Pathology department, University Hospital Son Espases, 07120, Mallorca, Spain., Hernández-Jover D; Radiology department, Sant Pau University Hospital, 08025, Barcelona, Spain., Gutierrez A; Hematology department, University Hospital Son Espases, 07120, Mallorca, Spain., Serrano C; Medical Oncology department, Vall d'Hebron University Hospital, 08035, Barcelona, Spain., Monteagudo M; Hereditary Endocrine Cancer Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain., Letón R; Hereditary Endocrine Cancer Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain., Robledo M; Hereditary Endocrine Cancer Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Institute of Health Carlos III (ISCIII), Madrid, Spain., Moura DS; Health Research Institute-Fundación Jiménez Díaz University Hospital, Universidad Autonoma de Madrid (IIS-FJD, UAM), 28040, Madrid, Spain., Martin-Ruiz M; Health Research Institute-Fundación Jiménez Díaz University Hospital, Universidad Autonoma de Madrid (IIS-FJD, UAM), 28040, Madrid, Spain., López-Guerrero JA; Molecular Biology department, Fundación Instituto Valenciano de Oncologia, 46009, Valencia, Spain., Cruz J; Pathology department, Fundación Instituto Valenciano de Oncologia, 46009, Valencia, Spain., Fernandez-Serra A; Molecular Biology department, Fundación Instituto Valenciano de Oncologia, 46009, Valencia, Spain., Blay JY; Medicine Department, Centre Léon Bérard, 69008, Lyon, France., Fumagalli E; Medicine Department, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133, Milan, Italy., Martinez-Marin V; Department of Medical Oncology, Hospital Universitario La Paz-IdiPAZ, P. Castellana, 261, 28046, Madrid, Spain.
المصدر: Molecular cancer [Mol Cancer] 2023 Aug 09; Vol. 22 (1), pp. 127. Date of Electronic Publication: 2023 Aug 09.
نوع المنشور: Clinical Trial, Phase II; Letter; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101147698 Publication Model: Electronic Cited Medium: Internet ISSN: 1476-4598 (Electronic) Linking ISSN: 14764598 NLM ISO Abbreviation: Mol Cancer Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : BioMed Central, c2002-
مواضيع طبية MeSH: Antineoplastic Agents*/therapeutic use , Gastrointestinal Stromal Tumors*/drug therapy , Gastrointestinal Stromal Tumors*/genetics , Sarcoma*/drug therapy, Adult ; Humans ; Mutation ; Protein Kinase Inhibitors/therapeutic use ; Proto-Oncogene Proteins c-kit/genetics
مستخلص: Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
Trial Registration: ClinicalTrials.gov Identifier: NCT02638766.
(© 2023. BioMed Central Ltd., part of Springer Nature.)
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فهرسة مساهمة: Keywords: Biomarker; Clinical trial; SDH: Regorafenib; Wild type GIST
سلسلة جزيئية: ClinicalTrials.gov NCT02638766
المشرفين على المادة: 0 (Antineoplastic Agents)
0 (Protein Kinase Inhibitors)
EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
24T2A1DOYB (regorafenib)
تواريخ الأحداث: Date Created: 20230809 Date Completed: 20230811 Latest Revision: 20231121
رمز التحديث: 20231121
مُعرف محوري في PubMed: PMC10413507
DOI: 10.1186/s12943-023-01832-9
PMID: 37559050
قاعدة البيانات: MEDLINE
الوصف
تدمد:1476-4598
DOI:10.1186/s12943-023-01832-9