@article{d63308bda17a4a04b1669d92c7d533ae,
title = "Reducing skin toxicities from egfr inhibitors with topical braf inhibitor therapy",
abstract = "Treatment of cancer with EGFR inhibitors is limited by on-target skin toxicities induced by inhibition of the MAPK pathway. BRAF inhibitors are known to paradoxically activate the MAPK downstream of EGFR, which we confirmed using human skin keratinocytes. We then conducted a phase I clinical trial testing the hypothesis that topical therapy with the BRAF inhibitor LUT014 could improve skin toxicities induced by EGFR inhibitors. Ten patients with metastatic colorectal cancer who had developed acneiform rash while being treated with cetuximab or panitumumab were enrolled in three cohorts. LUT014 was well tolerated, and there were no doselimiting toxicities. The acneiform rash improved in the 6 patients who started with grade 2 rash in the low and intermediate cohorts. We conclude that topical LUT014 is safe and efficacious in improving rash from EGFR inhibitors, consistent with the mechanism of action inducting paradoxical MAPK activation. Significance: BRAF inhibitor topical therapy could avoid dose reductions of EGFR inhibitors, locally treating the main dose-limiting skin toxicity of this class of agents.",
author = "Lacouture, {Mario E.} and Wainberg, {Zev A.} and Patel, {Anisha B.} and Anadkat, {Milan J.} and Stemmer, {Salomon M.} and Einat Shacham-Shmueli and Egmidio Medina and Galit Zelinger and Noa Shelach and Antoni Ribas",
note = "Funding Information: The authors want to thank the study patients and their families, the research teams at the different clinical trial institutions, and Smart Assays, Ness Ziona, Israel, for the conduct of the preclinical experiments. M.E. Lacouture was funded in part through NIH/ NIAMS grant U01 AR077511 and the NIH/NCI grant P30 CA008748. A. Ribas was supported by NIH grants R35 CA197633, P01 CA244118, and P30 CA016042 and the Ressler Family Fund. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Funding Information: The authors want to thank the study patients and their families, the research teams at the different clinical trial institutions, and Smart Assays, ness Ziona, Israel, for the conduct of the preclinical experiments. M.E. Lacouture was funded in part through nIH/ nIAMS grant U01 AR077511 and the nIH/nCI grant P30 CA008748. A. Ribas was supported by nIH grants R35 CA197633, P01 CA244118, and P30 CA016042 and the Ressler Family Fund. Publisher Copyright: {\textcopyright} 2021 The Authors; Published by theAmericanAssociation for Cancer Research.",
year = "2021",
month = sep,
doi = "10.1158/2159-8290.CD-20-1847",
language = "English",
volume = "11",
pages = "2158--2167",
journal = "Cancer discovery",
issn = "2159-8274",
number = "9",
}