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Liquid Biopsy–Based Test Appears Comparable to Standard Tissue Testing in Detecting BRAF V600 Mutations

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Key Points

  • Testing for BRAF V600 mutations in cell-free (cf) DNA from plasma using the polymerase chain reaction–based Idylla BRAF Mutation Test has acceptable concordance with standard testing of tumor tissue. The test has a 90-minute turnaround time and can predict therapy response over the course of treatment.
  • A higher percentage of mutant BRAF V600 in cfDNA corresponded with shorter overall survival in patients receiving BRAF/MEK inhibitors, as well as with a shorter time to treatment failure.
  • A decrease in the amount of BRAF-mutant cfDNA in sequentially collected plasma samples correlates with prolonged time to treatment failure.

Cell-free (cf) DNA from plasma offers a minimally invasive approach to obtain material for BRAF mutation analysis for diagnostics and response monitoring. A study by Janku et al investigating whether the detection of BRAF V600 mutations in plasma cfDNA from patients with advanced cancers using the polymerase chain reaction (PCR)-based Idylla BRAF Mutation Test was feasible has found that the test has acceptable concordance with standard testing of tumor tissue. In addition, the test has a 90-minute turnaround time and can predict response to therapy over the course of treatment. The study was published in Molecular Cancer Therapeutics.

Study Methodology

The current standard of care for BRAF mutation analysis is testing archival, formalin-fixed, paraffin-embedded (FFPE) tumor tissue. However, a lack of tissue samples often eliminates the possibility of mutation analysis, thereby limiting therapeutic options. In this study, the researchers used plasma samples collected from 160 patients with a range of advanced cancers with known BRAF V600 mutation status determined from archival paraffin-embedded tumor tissue samples obtained from routine diagnostic and/or therapeutic procedures from primary or metastatic sites.

The most common tumor types were colorectal cancer and melanoma. The researchers analyzed the blood samples for BRAF V600 mutations using a prototype version of the Idylla BRAF Mutation Test, a fully integrated real-time PCR-based test with a turnaround time of about 90 minutes.

Study Results

Of the 160 patients, BRAF V600 mutations were detected in 62 (39%) archival FFPE tumor samples and 47 (29%) plasma cfDNA samples. The two methods had overall agreement in 141 patients [88%; κ = 0.74; SE = 0.06; 95% confidence interval (CI) = 0.63–0.85]. Idylla had a sensitivity of 73% (95% CI = 0.60%–0.83%) and a specificity of 98% (95% CI = 0.93%–1.00%). A higher percentage, but not concentration, of BRAF V600 cfDNA in the wild-type background (> 2% vs ≤ 2%) was associated with shorter overall survival (P = .005) and in patients with BRAF mutations in the tissue, who were receiving BRAF/MEK inhibitors, and a shorter time to treatment failure (P = .001). Longitudinal monitoring demonstrated that decreasing levels of BRAF V600 cfDNA were associated with longer time to treatment failure (P = 0.045).

“We developed [the] Idylla BRAF Mutation Test, a full integrated quantitative allele-specific real-time PCR-based test that uses a single disposable cartridge,” said Filip Janku, MD, PhD, Assistant Professor of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center, in a statement. “We demonstrated that testing for BRAF V600 mutations in plasma cell-free DNA using this test is feasible, has comparable sensitivity and specificity to other PCR or next-generation sequencing methods, and has an unprecedented short turnaround time.”

“Our results suggest that high amounts of BRAF-mutant cell-free DNA before therapy is a negative prognostic biomarker for survival and outcomes of targeted therapy. It was somewhat counterintuitive since one would assume that more BRAF-mutant copies in the circulation would rather predict better outcomes with BRAF-targeted therapies. We also showed that a decrease in the amount of BRAF-mutant cell-free DNA in sequentially collected plasma samples correlates with better treatment outcomes.”

This study was funded by Biocartis, the Elsa U. Pardee Foundation, and the Sidney Kimmel Foundation for Cancer Research. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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