Subbiah, Vivek ORCID: 0000-0002-6064-6837, Puzanov, Igor, Blay, Jean-Yves ORCID: 0000-0001-7190-120X, Chau, Ian ORCID: 0000-0003-0286-8703, Lockhart, A. Craig, Raje, Noopur S., Wolf, Juergen, Baselga, Jose, Meric-Bernstam, Funda, Roszik, Jason ORCID: 0000-0002-4561-6170, Diamond, Eli L., Riely, Gregory J., Sherman, Eric J., Riehl, Todd, Pitcher, Bethany and Hyman, David M. (2020). Pan-Cancer Efficacy of Vemurafenib in BRAF(V)(600)-Mutant Non-Melanoma Cancers. Cancer Discov., 10 (5). S. 657 - 664. PHILADELPHIA: AMER ASSOC CANCER RESEARCH. ISSN 2159-8290

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Abstract

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 nonmelanoma BRAF(V)(600) 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(V)(600) 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Subbiah, VivekUNSPECIFIEDorcid.org/0000-0002-6064-6837UNSPECIFIED
Puzanov, IgorUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blay, Jean-YvesUNSPECIFIEDorcid.org/0000-0001-7190-120XUNSPECIFIED
Chau, IanUNSPECIFIEDorcid.org/0000-0003-0286-8703UNSPECIFIED
Lockhart, A. CraigUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Raje, Noopur S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wolf, JuergenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baselga, JoseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meric-Bernstam, FundaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roszik, JasonUNSPECIFIEDorcid.org/0000-0002-4561-6170UNSPECIFIED
Diamond, Eli L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Riely, Gregory J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sherman, Eric J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Riehl, ToddUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pitcher, BethanyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hyman, David M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-335477
DOI: 10.1158/2159-8290.CD-19-1265
Journal or Publication Title: Cancer Discov.
Volume: 10
Number: 5
Page Range: S. 657 - 664
Date: 2020
Publisher: AMER ASSOC CANCER RESEARCH
Place of Publication: PHILADELPHIA
ISSN: 2159-8290
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
OPEN-LABEL; BRAF; MELANOMA; INHIBITION; DABRAFENIB; TRAMETINIB; SURVIVAL; PHASE-2Multiple languages
OncologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/33547

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