Pan-cancer efficacy of vemurafenib in brafv600-mutant non-melanoma cancers

Vivek Subbiah, Igor Puzanov, Jean Yves Blay, Ian Chau, A. Craig Lockhart, Noopur S. Raje, Juergen Wolf, José Baselga, Funda Meric-Bernstam, Jason Roszik, Eli L. Diamond, Gregory J. Riely, Eric J. Sherman, Todd Riehl, Bethany Pitcher, David M. Hyman

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


BRAFV600 mutations occur in a wide range of tumor types, and RAF inhibition has become standard in several of these cancers. Despite this progress, BRAFV600 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 BRAFV600 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 car-cinomas. Collectively, these data demonstrate that single-agent BRAF inhibition has broader clinical activity than previously recognized. SIGNIFICANCE: These data suggest that BRAFV600 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.

Original languageEnglish (US)
Pages (from-to)657-663
Number of pages7
JournalCancer discovery
Issue number5
StatePublished - May 2020

ASJC Scopus subject areas

  • Oncology


Dive into the research topics of 'Pan-cancer efficacy of vemurafenib in braf<sup>v600</sup>-mutant non-melanoma cancers'. Together they form a unique fingerprint.

Cite this