@article{6dc2d713c821411ba2c98b3a3dd5aef0,
title = "Pan-cancer efficacy of vemurafenib in brafv600-mutant non-melanoma cancers",
abstract = "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.",
author = "Vivek Subbiah and Igor Puzanov and Blay, {Jean Yves} and Ian Chau and Lockhart, {A. Craig} and Raje, {Noopur S.} and Juergen Wolf and Jos{\'e} Baselga and Funda Meric-Bernstam and Jason Roszik and Diamond, {Eli L.} and Riely, {Gregory J.} and Sherman, {Eric J.} and Todd Riehl and Bethany Pitcher and Hyman, {David M.}",
note = "Funding Information: This study was supported by F. Hoffmann-La Roche Ltd. Additional support was provided by the NIH (P30 CA008748). J.-Y. Blay was funded in part by grants [NETSARC+ and LYRICAN (INCA-DGOS-INSERM 12563)]. Editorial support was provided by Lee Miller and Deirdre Carman, PhD, of Miller Medical Communications Ltd. funded by F. Hoffmann-La Roche Ltd. Funding Information: V. Subbiah is a scientific advisory board member at Helsinn, Loxo Oncology/Eli Lilly, R-Pharma US, INCYTE, QED, Medimmune, and Novartis, reports receiving commercial research grants from Roche/Genentech, Novartis, Pharmamar, Inhibrx, Exelixis, Blueprint Medicines, D3, Pfizer, MultiVir, Amgen, AbbVie, Alfa-Sigma, Bayer, Agensys, Boston Biomedical, Boston Pharmaceuticals, Turning Point Therapeutics, Idera, Loxo Oncology/Eli Lilly, Medimmune, Altum, Dragonfly Therapeutics, Takeda, GSK, Nanocarrier, Vegenics, North-west Biotherapeutics, Berg Health Pharma, Incyte, and Fujifilm, and has received other remuneration from Medscape, ASCO, and ESMO. I. Puzanov is a consultant at Amgen and has ownership interest (including patents) in Celldex. J.-Y. Blay reports receiving commercial research support from Roche Genentech, Novartis, and GSK, and has consultant/advisory board relationships with Novartis and Roche Genentech. I. Chau is an advisory board member at Bristol-Myers Squibb, Eli Lilly, MSD, Bayer, Roche, Merck Serono, Five Prime Therapeutics, AstraZeneca, Oncologie International, and Pierre Fabre. J. Wolf is an advisory board member for and has received a lecture fee from AbbVie, Amgen, MSD, Novartis, Pfizer, Roche, Takeda, AstraZeneca, BMS, Chugai, Janssen, Lilly, and Loxo, is an advisory board member at Blueprint, has received a lecture fee from Boehringer Ingelheim, and reports receiving commercial research grants from BMS, Johnson and Johnson, and Novartis. J. Baselga is EVP, Oncology R&D, at AstraZeneca, is a member of the board of directors at Foghorn, Varian, Bristol-Myers Squibb, Grail, Aura, and Infinity, is a consultant at PMV Pharma, Juno, and Seragon, reports receiving a commercial research grant from Roche, and has ownership interest (including patents) in Apogen, Tango, and Venthera. F. Meric-Bernstam is chair, Department of Investigational Cancer Therapeutics at MD Anderson Cancer Center, is a consultant at eFFECTOR Therapeutics, Samsung Bioepis, Aduro BioTech, Kolon Life Science, OrigiMed, Sumitomo Dainippon Pharma Co., Seattle Genetics Inc., Debiopharm, Dialectica, Piers Pharmaceuticals, Xencor, PACT Pharma, Zymeworks, Jackson Laboratory, Genen-tech, F. Hoffman-La Roche, Parexel International, Pfizer, and IBM Watson, reports receiving commercial research grants from Aileron Therapeutics, AstraZeneca, Guardant Health, K Group, Millennium Pharmaceuticals, Novartis, PPD Investigator Services, Puma Biotechnology, Seattle Genetics, Taiho Pharmaceutical, Zymeworks, Bayer Healthcare Pharmaceutical, Calithera Biosciences, Curis Inc., CytomX Therapeutics, Daiichi Sankyo, Debiopharm International, eFFECTOR Therapeutics, and Genentech Inc., has received speakers bureau honoraria from Sumitomo Dainippon Pharma and Dialectica, and has advisory board relationships with Puma Biotechnology, Mer-sana Therapeutics, Immunomedics, Silverback Therapeutics, Inflection Biosciences, Spectrum Pharmaceuticals, Seattle Genetics, Grail, Darwin Health, and Clearlight Diagnostics. E.L. Diamond has an advisory board relationship with Third Rock Ventures. G.J. Riely reports receiving commercial research grants from Roche, Takeda, Mirati, Pfizer, and Merck, and has advisory board relationships with Takeda, Merck, and Daiichi. E.J. Sherman is an advisory board member at Loxo, Regeneron, Novartis, and Eisai. T. Riehl is a clinical scientist at Roche/Genentech. B. Pitcher is a senior statistical scientist at Hoffmann-La Roche Limited. D.M Hyman is chief medical officer at Eli Lilly/Loxo Oncology, is a consultant at Chugai Pharma, Boehringer Ingelheim, Pfizer, Bayer, Genentech/Roche, and Eli Lilly, is a scientific advisory board member at Kinnate, and reports receiving commercial research grants from Astra-Zeneca, Puma Biotechnology, Loxo Oncology, and Bayer. No potential conflicts of interest were disclosed by the other authors.",
year = "2020",
month = may,
doi = "10.1158/2159-8290.CD-19-1265",
language = "English (US)",
volume = "10",
pages = "657--663",
journal = "Cancer Discovery",
issn = "2159-8274",
publisher = "American Association for Cancer Research Inc.",
number = "5",
}