Sistema de Salut de Catalunya
Institut Català de la Salut
[Subbiah V] Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. [Kreitman RJ] Laboratory of Molecular Biology, National Institutes of Health, Bethesda, MD, USA. [Wainberg ZA] Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. [Gazzah A] Drug Development Department (DITEP), Gustave Roussy Cancer Institute, Villejuif, France. [Lassen U] Department of Oncology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. [Stein A] Department of Internal Medicine II (Oncology Center), University Medical Center Hamburg-Eppendorf, Hamburg, Germany. [Elez Fernandez E] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. IOB-Quiron, UVic-UCC, Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2023-07-05T07:57:22Z
2023-07-05T07:57:22Z
2023-05
Outcomes research; Clinical trial design
Recerca de resultats; Disseny d'assaig clínic
Investigación de resultados; Diseño de ensayo clínico
BRAFV600E alterations are prevalent across multiple tumors. Here we present final efficacy and safety results of a phase 2 basket trial of dabrafenib (BRAF kinase inhibitor) plus trametinib (MEK inhibitor) in eight cohorts of patients with BRAFV600E-mutated advanced rare cancers: anaplastic thyroid carcinoma (n = 36), biliary tract cancer (n = 43), gastrointestinal stromal tumor (n = 1), adenocarcinoma of the small intestine (n = 3), low-grade glioma (n = 13), high-grade glioma (n = 45), hairy cell leukemia (n = 55) and multiple myeloma (n = 19). The primary endpoint of investigator-assessed overall response rate in these cohorts was 56%, 53%, 0%, 67%, 54%, 33%, 89% and 50%, respectively. Secondary endpoints were median duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety. Median DoR was 14.4 months, 8.9 months, not reached, 7.7 months, not reached, 31.2 months, not reached and 11.1 months, respectively. Median PFS was 6.7 months, 9.0 months, not reached, not evaluable, 9.5 months, 5.5 months, not evaluable and 6.3 months, respectively. Median OS was 14.5 months, 13.5 months, not reached, 21.8 months, not evaluable, 17.6 months, not evaluable and 33.9 months, respectively. The most frequent (≥20% of patients) treatment-related adverse events were pyrexia (40.8%), fatigue (25.7%), chills (25.7%), nausea (23.8%) and rash (20.4%). The encouraging tumor-agnostic activity of dabrafenib plus trametinib suggests that this could be a promising treatment approach for some patients with BRAFV600E-mutated advanced rare cancers. ClinicalTrials.gov registration: NCT02034110.
Article
Published version
English
Càncer - Tractament; Quimioteràpia combinada; Anomalies cromosòmiques; DISEASES::Neoplasms; Other subheadings::Other subheadings::Other subheadings::/drug therapy; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols; PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation; ENFERMEDADES::neoplasias; Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada; FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación
Nature Portfolio
Nature Medicine;29
https://doi.org/10.1038/s41591-023-02321-8
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
Articles científics - HVH [3440]
