Intermittent BRAF inhibition in advanced BRAF mutated melanoma results of a phase II randomized trial
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- dc.contributor.author González Cao, María
- dc.contributor.author Montagut Viladot, Clara
- dc.contributor.author Berrocal Jaime, Alfonso
- dc.date.accessioned 2022-09-15T07:13:38Z
- dc.date.available 2022-09-15T07:13:38Z
- dc.date.issued 2021
- dc.description.abstract Combination treatment with BRAF (BRAFi) plus MEK inhibitors (MEKi) has demonstrated survival benefit in patients with advanced melanoma harboring activating BRAF mutations. Previous preclinical studies suggested that an intermittent dosing of these drugs could delay the emergence of resistance. Contrary to expectations, the first published phase 2 randomized study comparing continuous versus intermittent schedule of dabrafenib (BRAFi) plus trametinib (MEKi) demonstrated a detrimental effect of the "on-off" schedule. Here we report confirmatory data from the Phase II randomized open-label clinical trial comparing the antitumoral activity of the standard schedule versus an intermittent combination of vemurafenib (BRAFi) plus cobimetinib (MEKi) in advanced BRAF mutant melanoma patients (NCT02583516). The trial did not meet its primary endpoint of progression free survival (PFS) improvement. Our results show that the antitumor activity of the experimental intermittent schedule of vemurafenib plus cobimetinib is not superior to the standard continuous schedule. Detection of BRAF mutation in cell free tumor DNA has prognostic value for survival and its dynamics has an excellent correlation with clinical response, but not with progression. NGS analysis demonstrated de novo mutations in resistant cases.
- dc.format.mimetype application/pdf
- dc.identifier.citation González-Cao M, Mayo de Las Casas C, Oramas J, Berciano-Guerrero MA, de la Cruz L, Cerezuela P, et al. Intermittent BRAF inhibition in advanced BRAF mutated melanoma results of a phase II randomized trial. Nat Commun. 2021 Dec 1; 12(1): 7008. DOI: 10.1038/s41467-021-26572-6
- dc.identifier.doi http://dx.doi.org/10.1038/s41467-021-26572-6
- dc.identifier.issn 2041-1723
- dc.identifier.uri http://hdl.handle.net/10230/54072
- dc.language.iso eng
- dc.publisher Nature Research
- dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/765492
- dc.rights Copyright © González-Cao M, Mayo de Las Casas C, Oramas J, Berciano-Guerrero MA, de la Cruz L, Cerezuela P. 2021.Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.other Melanoma -- Tractament
- dc.subject.other Càncer
- dc.title Intermittent BRAF inhibition in advanced BRAF mutated melanoma results of a phase II randomized trial
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion