Kaley, Thomas, Touat, Mehdi, Subbiah, Vivek ORCID: 0000-0002-6064-6837, Hollebecque, Antoine, Rodon, Jordi, Lockhart, A. Craig, Keedy, Vicki, Bielle, Franck, Hofheinz, Ralf-Dieter, Joly, Florence, Blay, Jean-Yves ORCID: 0000-0001-7190-120X, Chau, Ian, Puzanov, Igor, Raje, Noopur S., Wolf, Jurgen, DeAngelis, Lisa M., Makrutzki, Martina, Riehl, Todd, Pitcher, Bethany, Baselga, Jose and Hyman, David M. (2018). BRAF Inhibition in BRAF(V600)-Mutant Gliomas: Results From the VE-BASKET Study. J. Clin. Oncol., 36 (35). S. 3477 - 3487. ALEXANDRIA: AMER SOC CLINICAL ONCOLOGY. ISSN 1527-7755

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Abstract

Purpose BRAF(V600) mutations are frequently found in several glioma subtypes, including pleomorphic xanthoastrocytoma (PXA) and ganglioglioma and much less commonly in glioblastoma. We sought to determine the activity of vemurafenib, a selective inhibitor of BRAF(V600), in patients with gliomas that harbor this mutation. Patients and Methods The VE-BASKET study was an open-label, nonrandomized, multicohort study for BRAF(V600)-mutant nonmelanoma cancers. Patients with BRAF(V600)-mutant glioma received vemurafenib 960 mg twice per day continuously until disease progression, withdrawal, or intolerable adverse effects. Key end points included confirmed objective response rate by RECIST version 1.1, progression-free survival, overall survival, and safety. Results Twenty-four patients (median age, 32 years; 18 female and six male patients) with glioma, including malignant diffuse glioma (n = 11; six glioblastoma and five anaplastic astrocytoma), PXA (n = 7), anaplastic ganglioglioma (n = 3), pilocytic astrocytoma (n = 2), and high-grade glioma, not otherwise specified (n = 1), were treated. Confirmed objective response rate was 25% (95% CI, 10% to 47%) and median progression-free survival was 5.5 months (95% CI, 3.7 to 9.6 months). In malignant diffuse glioma, best response included one partial response and five patients with stable disease, two of whom had disease stabilization that lasted more than 1 year. In PXA, best response included one complete response, two partial responses, and three patients with stable disease. Additional partial responses were observed in patients with pilocytic astrocytoma and anaplastic ganglioglioma (one each). The safety profile of vemurafenib was generally consistent with that of previously published studies. Conclusion Vemurafenib demonstrated evidence of durable antitumor activity in some patients with BRAF(V600)-mutant gliomas, although efficacy seemed to vary qualitatively by histologic subtype. Additional study is needed to determine the optimal use of vemurafenib in patients with primary brain tumors and to identify the mechanisms driving differential responses across histologic subsets. (c) 2018 by American Society of Clinical Oncology. Creative Commons Attribution Non-Commercial No Derivatives 4.0 License: https://creativecommons.org/licenses/by-nc-nd/4.0/

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Kaley, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Touat, MehdiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Subbiah, VivekUNSPECIFIEDorcid.org/0000-0002-6064-6837UNSPECIFIED
Hollebecque, AntoineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rodon, JordiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lockhart, A. CraigUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Keedy, VickiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bielle, FranckUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hofheinz, Ralf-DieterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Joly, FlorenceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blay, Jean-YvesUNSPECIFIEDorcid.org/0000-0001-7190-120XUNSPECIFIED
Chau, IanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Puzanov, IgorUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Raje, Noopur S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wolf, JurgenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
DeAngelis, Lisa M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Makrutzki, MartinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Riehl, ToddUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pitcher, BethanyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baselga, JoseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hyman, David M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-162224
DOI: 10.1200/JCO.2018.78.9990
Journal or Publication Title: J. Clin. Oncol.
Volume: 36
Number: 35
Page Range: S. 3477 - 3487
Date: 2018
Publisher: AMER SOC CLINICAL ONCOLOGY
Place of Publication: ALEXANDRIA
ISSN: 1527-7755
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
DABRAFENIB PLUS TRAMETINIB; CELL LUNG-CANCER; OPEN-LABEL; RESPONSE ASSESSMENT; PROGNOSTIC-FACTORS; MUTANT BRAF; VEMURAFENIB; BEVACIZUMAB; RECURRENT; PHASE-2Multiple languages
OncologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/16222

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