The Use of ctDNA for BRAF Mutation Testing in Routine Clinical Practice in Patients with Advanced Melanoma

SIMPLE SUMMARY: Assessment of BRAF mutation status is mandatory in advanced, previously untreated melanoma patients since it is present in 40–50% of cases and allows treatment with specific inhibitors. The testing is usually performed on the primary tumor or metastatic lesion; however, in some cases, liquid biopsy and analysis of circulating tumor DNA in the blood can be used. The aim of our study was to evaluate the clinical utility of plasma circulating tumor DNA analysis for BRAF mutation. We identified 46 patients (21 female, 25 male) who underwent such a procedure. A BRAF mutation was found in 45.7% of liquid biopsies and 44.8% of tissue samples. In 18 patients, therapy with BRAF/MEK inhibitors was initiated on the basis of the result of liquid biopsy. Our study confirms the clinical utility of BRAF mutation detection in liquid biopsy. ABSTRACT: Assessment of BRAF mutation status is mandatory in advanced, treatment-naïve melanoma patients. Liquid biopsy can be an alternative in cases with inadequate or unavailable tumor tissue. The aim of our study was to evaluate the clinical utility of plasma circulating tumor DNA analysis for BRAF mutation testing and to assess outcomes of therapy with BRAF/MEK inhibitors initiated based on the liquid biopsy results. This was a retrospective single-center analysis of 46 patients (21 female, 25 male) with advanced melanoma who underwent circulating tumor DNA (ctDNA) BRAF mutation testing. A BRAF mutation was found in 45.7% (21/46) of liquid biopsies and 44.8% (13/29) of tissue samples. In patients with both ctDNA and tissue samples (n = 29), the concordance between the results of both tests was 82.8%. A BRAF mutation was detected in 7/17 (41.2%) patients with only ctDNA analysis. In 18 patients, therapy with BRAF/MEK inhibitors was initiated on the basis of the result of liquid biopsy. The objective response rate was 77.8 %, and the median PFS was 6.0 months. Our study confirms the clinical utility of BRAF mutation detection in plasma ctDNA. This study provides initial real-world data showing that treatment with BRAF/MEK inhibitors could be commenced based on liquid biopsy results.