• F Loupakis, C Cremolini, L Salvatore, G Masi, E Sensi, M Schirripa, A Michelucci, E Pfanner, I Brunetti, C Lupi, C Antoniotti, F Bergamo, S Lonardi, V Zagonel, P Simi, G Fontanini, and A Falcone.
• Unit of Medical Oncology 2, Azienda Ospedaliera-Universitaria Pisana, Via Roma 67, 56126 Pisa, Italy. Electronic address: fotiosloupakis@gmail.com.
• Eur. J. Cancer. 2014 Jan 1; 50 (1): 57-63.

BackgroundBRAF V600E mutation plays a negative prognostic role in metastatic colorectal cancer (mCRC), leading to a median Progression Free Survival (PFS) of 4-6months with first-line conventional treatments. Our group recently reported in a retrospective exploratory analysis of a phase II trial that FOLFOXIRI (5-FU/LV+Oxaliplatin+Irinotecan) plus bevacizumab might allow to achieve remarkable results in terms of PFS and Overall Survival (OS) also in this poor-prognosis subgroup. The aim of this work was to prospectively validate our retrospective finding.Patients And MethodsThis phase II trial was designed to detect an increase in 6month-Progression Free Rate (6m-PFR) from 45% to 80% in a population of BRAF mutant mCRC patients treated with first-line FOLFOXIRI plus bevacizumab. Secondary end-points were PFS, OS, response rate (RR) and the analysis of outcome parameters in the pooled population consisting of both retrospectively and prospectively included patients. This trial is registered with ClinicalTrials.gov, number NCT01437618.ResultsTwo-hundred-fourteen potentially eligible mCRC patients were screened for BRAF mutational status. Fifteen BRAF mutant patients (7%) were included in the validation cohort. At a median follow up of 25.7months, 6m-PFR was 73%. Median PFS and OS were 9.2 and 24.1months, respectively. In the pooled population, at a median follow up of 40.4months, 6m-PFR was 84%. Median PFS and OS were 11.8 and 24.1months, respectively. Overall RR and disease control rate were 72% and 88%, respectively.ConclusionLacking randomised trials in this specific molecular subgroup, FOLFOXIRI plus bevacizumab might be a reasonable option for the first-line treatment of BRAF mutant mCRC patients.Copyright © 2013 Elsevier Ltd. All rights reserved.

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