Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Subbiah, Vivek UNSPECIFIED orcid.org/0000-0002-6064-6837 UNSPECIFIED Puzanov, Igor UNSPECIFIED UNSPECIFIED UNSPECIFIED Blay, Jean-Yves UNSPECIFIED orcid.org/0000-0001-7190-120X UNSPECIFIED Chau, Ian UNSPECIFIED orcid.org/0000-0003-0286-8703 UNSPECIFIED Lockhart, A. Craig UNSPECIFIED UNSPECIFIED UNSPECIFIED Raje, Noopur S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wolf, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Baselga, Jose UNSPECIFIED UNSPECIFIED UNSPECIFIED Meric-Bernstam, Funda UNSPECIFIED UNSPECIFIED UNSPECIFIED Roszik, Jason UNSPECIFIED orcid.org/0000-0002-4561-6170 UNSPECIFIED Diamond, Eli L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Riely, Gregory J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sherman, Eric J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Riehl, Todd UNSPECIFIED UNSPECIFIED UNSPECIFIED Pitcher, Bethany UNSPECIFIED UNSPECIFIED UNSPECIFIED Hyman, David M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language OPEN-LABEL; BRAF; MELANOMA; INHIBITION; DABRAFENIB; TRAMETINIB; SURVIVAL; PHASE-2 Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/33547