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BRAF Inhibition in BRAFV600-Mutant Gliomas: Results From the VE-BASKET Study
Thomas Kaley1, Mehdi Touat1, Vivek Subbiah1
1Thomas Kaley, Lisa M. DeAngelis, Jose Baselga, and David M. Hyman, Memorial Sloan Kettering Cancer Center; Thomas Kaley, Lisa M. DeAngelis, Jose Baselga, and David M. Hyman, Weill Cornell Medical College, New York; Igor Puzanov, Roswell Park Cancer Institute, Buffalo, NY; Mehdi Touat and Antoine Hollebecque, Institut Gustave Roussy, Villejuif; Franck Bielle, Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, Paris; Florence Joly, Centre François Baclesse, Caen; Jean-Yves Blay, Centre Léon Bérard, Lyon, France; Vivek Subbiah, MD Anderson Cancer Center, Houston, TX; Jordi Rodon, Vall d'Hebron University Hospital, Barcelona, Spain; A. Craig Lockhart, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL; Vicki Keedy, Vanderbilt University Medical Center, Nashville, TN; Ralf-Dieter Hofheinz, Universitätsmedizin Mannheim, Mannheim; Jurgen Wolf, Universitätsklinikum Köln, Cologne, Germany; Ian Chau, The Royal Marsden National Health Service Foundation Trust, London, United Kingdom; Noopur S. Raje, Massachusetts General Hospital, Boston, MA; Martina Makrutzki, F Hoffmann-La Roche, Basel, Switzerland; Todd Riehl, Genentech, South San Francisco, CA; and Bethany Pitcher, F Hoffmann-La Roche, Mississauga, Ontario, Canada.
Purpose:
BRAFV600 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 BRAFV600, in patients with gliomas that harbor this mutation.
Patients And Methods:
The VE-BASKET study was an open-label, nonrandomized, multicohort study for BRAFV600-mutant nonmelanoma cancers. Patients with BRAFV600-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 BRAFV600-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.
Insights
Vemurafenib showed antitumor activity in BRAF V600-mutant gliomas, with responses varying by subtype. Further research is needed to optimize its use in brain tumors.
Area of Science:
- Neuro-oncology
- Molecular oncology
- Clinical trials
Background:
- BRAF V600 mutations are prevalent in pleomorphic xanthoastrocytoma and ganglioglioma, and less common in glioblastoma.
- Vemurafenib is a targeted therapy inhibiting BRAF V600 mutations.
Purpose of the Study:
- To evaluate the efficacy and safety of vemurafenib in patients with BRAF V600-mutant gliomas.
- To determine the objective response rate and progression-free survival in this patient cohort.
Main Methods:
- The VE-BASKET study enrolled patients with BRAF V600-mutant gliomas.
- Patients received vemurafenib 960 mg twice daily until disease progression or intolerance.
- Response was assessed using RECIST v1.1 criteria.
Main Results:
- Twenty-four patients with various glioma subtypes were treated.
- The confirmed objective response rate was 25%, with a median progression-free survival of 5.5 months.
- Durable responses were observed in pleomorphic xanthoastrocytoma and malignant diffuse glioma subtypes.
Conclusions:
- Vemurafenib demonstrated durable antitumor activity in select BRAF V600-mutant gliomas.
- Efficacy varied by glioma histologic subtype, necessitating further investigation.
- Additional studies are required to define optimal use and understand differential responses.
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