Tumor-specific circulating cell-free DNA (cfDNA) BRAF mutations (muts) to predict clinical outcome in patients (pts) treated with the BRAF inhibitor dabrafenib (GSK2118436).

8518 Background: Tumor specific cfDNA levels in blood increase with tumor burden and decrease following treatment. cfDNA can harbor muts consistent with the tumor. Thus cfDNA could be a useful biomarker of therapeutic response. BREAK-2, an open label, single arm, Phase II study evaluated efficacy, safety and tolerability of dabrafenib in BRAF V600E/K mut+ metastatic melanoma pts. Exploratory objectives of BREAK-2 were to evaluate whether (i) tumor and cfDNA BRAF muts are correlated; (ii) cfDNA levels correlate with baseline tumor burden and (iii) cfDNA muts predict clinical outcome with dabrafenib. Methods: BRAF mut status was established for 92pts using an allele-specific PCR assay in tumor samples. Baseline plasma samples were available for 91/92 pts. cfDNA BRAF mut status was evaluated by Inostics GmBH using the BEAMing technology. Spearman correlation coefficients (R) were used to determine the association between cfDNA fraction (mut DNA molecules > 0.01%) and estimated baseline tumor burden, calculat...