Re-challenge with BRAF-directed treatment: A multi-institutional retrospective study.

9512Background: Most patients treated with BRAF inhibitors (BRAFi) +/- MEK inhibitors (MEKi) eventually progress on treatment. Along with genetic acquired resistance, epigenetic mechanisms that could be reversed after BRAFi discontinuation have been described. The purpose of this study was to analyse outcomes for patients (pts) retreated with BRAF-directed therapy. Methods: 116 pts who received BRAFi based therapy and, after a break, were re-challenged with BRAFi +/- MEKi treated at 14 centres in Europe, US, and Australia were analysed for progression free survival (PFS) and response rate (RR), as well as factors predicting overall survival (OS) (demographics, disease stage, treatment, LDH level, duration of first BRAFi treatment, reason for first BRAFi discontinuation and interval between BRAFi stop and re-challenge). Multivariate Cox regression, regression trees and Kaplan Meier method were used. Results: Median duration of 1st BRAFi +/- MEKi treatment was 9.4 months (mts) and 7.7 mts for the subsequent...