Pan-Cancer Efficacy of Vemurafenib in BRAF V600-Mutant Non-Melanoma Cancers.
Cancer Discov
; 10(5): 657-663, 2020 05.
Article
en En
| MEDLINE
| ID: mdl-32029534
BRAF V600 mutations occur in a wide range of tumor types, and RAF inhibition has become standard in several of these cancers. Despite this progress, BRAF V600 mutations have historically been considered a clear demonstration of tumor lineage context-dependent oncogene addiction, based predominantly on the insensitivity to RAF inhibition in colorectal cancer. However, the true broader activity of RAF inhibition pan-cancer remains incompletely understood. To address this, we conducted a multicohort "basket" study of the BRAF inhibitor vemurafenib in non-melanoma BRAF V600 mutation-positive solid tumors. In total, 172 patients with 26 unique cancer types were treated, achieving an overall response rate of 33% and median duration of response of 13 months. Responses were observed in 13 unique cancer types, including historically treatment-refractory tumor types such as cholangiocarcinoma, sarcoma, glioma, neuroendocrine carcinoma, and salivary gland carcinomas. Collectively, these data demonstrate that single-agent BRAF inhibition has broader clinical activity than previously recognized. SIGNIFICANCE: These data suggest that BRAF V600 mutations lead to oncogene addiction and are clinically actionable in a broad range of non-melanoma cancers, including tumor types in which RAF inhibition is not currently considered standard of care.See related commentary by Ribas and Lo, p. 640.This article is highlighted in the In This Issue feature, p. 627.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Proto-Oncogénicas B-raf
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Vemurafenib
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Neoplasias
Límite:
Adolescent
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Adult
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Aged
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Aged80
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Humans
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Middle aged
Idioma:
En
Revista:
Cancer Discov
Año:
2020
Tipo del documento:
Article
Pais de publicación:
Estados Unidos