BRAF inhibition in BRAFV600-mutant gliomas: Results from the VE-BASKET study

Thomas Kaley, Mehdi Touat, Vivek Subbiah, Antoine Hollebecque, Jordi Rodon, Albert Lockhart, Vicki Keedy, Franck Bielle, Ralf Dieter Hofheinz, Florence Joly, Jean Yves Blay, Ian Chau, Igor Puzanov, Noopur S. Raje, Jurgen Wolf, Lisa M. DeAngelis, Martina Makrutzki, Todd Riehl, Bethany Pitcher, Jose BaselgaDavid M. Hyman

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3477-3484
Number of pages8
JournalJournal of Clinical Oncology
Volume36
Issue number35
DOIs
StatePublished - Dec 10 2018

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Glioma
Ganglioglioma
Astrocytoma
Glioblastoma
Disease-Free Survival
Safety
Mutation
Brain Neoplasms
Disease Progression
PLX4032
Survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Kaley, T., Touat, M., Subbiah, V., Hollebecque, A., Rodon, J., Lockhart, A., ... Hyman, D. M. (2018). BRAF inhibition in BRAFV600-mutant gliomas: Results from the VE-BASKET study. Journal of Clinical Oncology, 36(35), 3477-3484. https://doi.org/10.1200/JCO.2018.78.9990

BRAF inhibition in BRAFV600-mutant gliomas : Results from the VE-BASKET study. / Kaley, Thomas; Touat, Mehdi; Subbiah, Vivek; Hollebecque, Antoine; Rodon, Jordi; Lockhart, Albert; Keedy, Vicki; Bielle, Franck; Hofheinz, Ralf Dieter; Joly, Florence; Blay, Jean Yves; Chau, Ian; Puzanov, Igor; Raje, Noopur S.; Wolf, Jurgen; DeAngelis, Lisa M.; Makrutzki, Martina; Riehl, Todd; Pitcher, Bethany; Baselga, Jose; Hyman, David M.

In: Journal of Clinical Oncology, Vol. 36, No. 35, 10.12.2018, p. 3477-3484.

Research output: Contribution to journalArticle

Kaley, T, Touat, M, Subbiah, V, Hollebecque, A, Rodon, J, Lockhart, A, Keedy, V, Bielle, F, Hofheinz, RD, Joly, F, Blay, JY, Chau, I, Puzanov, I, Raje, NS, Wolf, J, DeAngelis, LM, Makrutzki, M, Riehl, T, Pitcher, B, Baselga, J & Hyman, DM 2018, 'BRAF inhibition in BRAFV600-mutant gliomas: Results from the VE-BASKET study', Journal of Clinical Oncology, vol. 36, no. 35, pp. 3477-3484. https://doi.org/10.1200/JCO.2018.78.9990
Kaley, Thomas ; Touat, Mehdi ; Subbiah, Vivek ; Hollebecque, Antoine ; Rodon, Jordi ; Lockhart, Albert ; Keedy, Vicki ; Bielle, Franck ; Hofheinz, Ralf Dieter ; Joly, Florence ; Blay, Jean Yves ; Chau, Ian ; Puzanov, Igor ; Raje, Noopur S. ; Wolf, Jurgen ; DeAngelis, Lisa M. ; Makrutzki, Martina ; Riehl, Todd ; Pitcher, Bethany ; Baselga, Jose ; Hyman, David M. / BRAF inhibition in BRAFV600-mutant gliomas : Results from the VE-BASKET study. In: Journal of Clinical Oncology. 2018 ; Vol. 36, No. 35. pp. 3477-3484.
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abstract = "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.",
author = "Thomas Kaley and Mehdi Touat and Vivek Subbiah and Antoine Hollebecque and Jordi Rodon and Albert Lockhart and Vicki Keedy and Franck Bielle and Hofheinz, {Ralf Dieter} and Florence Joly and Blay, {Jean Yves} and Ian Chau and Igor Puzanov and Raje, {Noopur S.} and Jurgen Wolf and DeAngelis, {Lisa M.} and Martina Makrutzki and Todd Riehl and Bethany Pitcher and Jose Baselga and Hyman, {David M.}",
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T1 - BRAF inhibition in BRAFV600-mutant gliomas

T2 - Results from the VE-BASKET study

AU - Kaley, Thomas

AU - Touat, Mehdi

AU - Subbiah, Vivek

AU - Hollebecque, Antoine

AU - Rodon, Jordi

AU - Lockhart, Albert

AU - Keedy, Vicki

AU - Bielle, Franck

AU - Hofheinz, Ralf Dieter

AU - Joly, Florence

AU - Blay, Jean Yves

AU - Chau, Ian

AU - Puzanov, Igor

AU - Raje, Noopur S.

AU - Wolf, Jurgen

AU - DeAngelis, Lisa M.

AU - Makrutzki, Martina

AU - Riehl, Todd

AU - Pitcher, Bethany

AU - Baselga, Jose

AU - Hyman, David M.

PY - 2018/12/10

Y1 - 2018/12/10

N2 - 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.

AB - 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.

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