Sustained Tumor Control With MAPK Inhibition in BRAF V600-Mutant Adult Glial and Glioneuronal Tumors.
Neurology
; 97(7): e673-e683, 2021 08 17.
Article
em En
| MEDLINE
| ID: mdl-34088874
ABSTRACT
OBJECTIVE:
To assess whether RAF and MEK inhibitors (RAFi/MEKi) can provide long-term clinical benefit in adult patients with BRAF V600-mutant glial and glioneuronal tumors (GGNTs), we analyzed tumor response and long-term outcome in a retrospective cohort.METHODS:
We performed a retrospective search in the institutional databases of 6 neuro-oncology departments for adult patients with recurrent or disseminated BRAF V600-mutant GGNTs treated with RAFi/MEKi.RESULTS:
Twenty-eight adults with recurrent or disseminated BRAF V600-mutant gangliogliomas (n = 9), pleomorphic xanthoastrocytomas (n = 9), and diffuse gliomas (n = 10) were included in the study. At the time that treatment with RAFi/MEKi was started, all tumors displayed radiologic features of high-grade neoplasms. Thirteen patients received RAFi as single agents (vemurafenib [n = 11], dabrafenib [n = 2]), and 15 received combinations of RAFi/MEKi (vemurafenib + cobimetinib [n = 5], dabrafenib + trametinib [n = 10]). Eleven patients achieved a partial or complete response (11 of 28, 39%), with a median reduction of -78% in their tumor burden. Responders experienced a median increase of 10 points in their Karnofsky Performance Status (KPS) score and a median progression-free survival of 18 months, which was longer than achieved with first-line treatment (i.e., 7 months, p = 0.047). Responders had better KPS score (p = 0.018) and tended to be younger (p = 0.061) and to be treated earlier (p = 0.099) compared to nonresponders. Five patients were rechallenged with RAFi/MEKi at progression, with novel tumor responses in 2. On univariate and multivariate analyses, response to RAFi/MEKi was an independent predictor of overall survival.CONCLUSIONS:
Our study highlights the long-term clinical benefits of RAFi/MEKi in adult patients with BRAF V600-mutant GGNTs and encourages rechallenge in responders. CLASSIFICATION OF EVIDENCE This study provides Class III evidence that, for adult patients with BRAF V600-mutant GGNT, RAFi/MEKi can reduce tumor burden and provide clinical benefit.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Encefálicas
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Avaliação de Resultados em Cuidados de Saúde
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Quinases de Proteína Quinase Ativadas por Mitógeno
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Proteínas Proto-Oncogênicas B-raf
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Inibidores de Proteínas Quinases
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Glioma
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article