RT Journal Article
T1 Intermittent BRAF inhibition in advanced BRAF mutated melanoma results of a phase II randomized trial
A1 Gonzalez-Cao, Maria
A1 Mayo Casas, Clara
A1 Oramas, Juana
A1 Berciano-Guerrero, Miguel A.
A1 de la Cruz, Luis
A1 Cerezuela, Pablo
A1 Arance, Ana
A1 Munoz-Couselo, Eva
A1 Espinosa, Enrique
A1 Puertolas, Teresa
A1 Diaz Beveridge, Roberto
A1 Ochenduszko, Sebastian
A1 Villanueva, Maria-Jose
A1 Basterretxea, Laura
A1 Bellido, Lorena
A1 Rodriguez, Delvys
A1 Campos, Begona
A1 Montagut, Clara
A1 Drozdowskyj, Ana
A1 Molina, Miguel A.
A1 Antonio Lopez-Martin, Jose
A1 Berrocal, Alfonso
K1 Mek inhibition
K1 Double-blind
K1 Vemurafenib
K1 Efficacy
AB 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.Whether intermittent strategies of delivering drugs can improve cancer patients survival is still unclear. Here, the authors reports the results of a randomized phase II clinical trial aimed to compare the efficacy and safety of two dosing regimens (continuous and intermittent) of vemurafenib and cobimetinib combination as first-line treatment of patients with unresectable or metastatic advanced melanoma with BRAFV600 mutation
PB Nature portfolio
YR 2021
FD 2021-12-01
LK https://hdl.handle.net/10668/27003
UL https://hdl.handle.net/10668/27003
LA en
DS RISalud
RD Apr 6, 2025