Liquid Biopsy Found Comparable to Standard Tissue Biopsy in Identifying BRAF V600 Mutation Status
Plasma from a blood draw can be used to test for BRAF V600 mutations in advanced cancers in just 90 minutes, and results were comparable to using tissue biopsy. Testing for BRAF V600 mutations can predict responses to therapies that target these mutations.1
“Cell-free DNA is released to the circulation from cancer cells undergoing apoptosis or necroptosis in the primary or metastatic cancer lesions and can be detected in the blood,” said Filip Janku, MD, PhD, assistant professor of Investigational Cancer Therapeutics (Phase I Clinical Trials Program) at The University of Texas MD Anderson Cancer Center in Houston. This study used the Idylla BRAF mutation test, which is based on polymerase chain reaction (PCR). Idylla is a system made by Biocartis, the sponsor of the study.
“Unlike performing tissue biopsies, obtaining blood samples to isolate cell-free DNA is a minimally invasive approach with less risk to the patients at a lower cost. The samples can be collected at multiple time points and provide valuable information about the genetic changes that occur during the course of the disease, as this is not a static process,” he added.
The study used plasma samples collected from 160 patients with advanced cancer; colorectal cancer and melanoma were the most common tumor types. BRAF V600 mutation status was already determined using paraffin-embedded tumor tissue samples. The researchers used the Idylla system to analyze samples of the patients' blood plasma.
Concordance between the standard tests using the paraffin-embedded tissues and the liquid samples collected at baseline was 88%. When samples were collected at any time point during treatment, concordance between tissue biopsy and liquid biopsy was 90%.
The liquid biopsy had 73% sensitivity, 98% specificity, and a positive-predictive value of 96% (a positive result was correctly predicted 96 of 100 times); negative-predictive value was 85% (a negative result was correctly predicted 85 of 100 times).
The amount of BRAF V600 mutant cell-free DNA was predictive of overall survival for the patients, as detected by the Idylla system. Survival was 10.7 months for 2% or less BRAF-mutant cell-free DNA and 4.4 months for those with more than 2% of BRAF V600 mutations in the patients' samples.
Presence of BRAF V600 mutations at baseline was predictive of time to failure of treatment with BRAF and/or MEK inhibitors: 13.1 months for patients who were negative for BRAF V600 mutation at baseline samples vs 3 months for patients who were positive for BRAF V600 mutation at baseline.
“We developed Idylla BRAF Mutation Test, a fully integrated quantitative allele-specific real-time PCR-based test that uses a single disposable cartridge. 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,” Janku said.
“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,” Janku said. “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.”
1. Janku F, Huang HJ, Claes B, et al. BRAF mutation testing in cell-free DNA from the plasma of patients with advanced cancers using a rapid, automated molecular diagnostics system [published online May 20, 2016]. Mol Cancer Ther. doi:10.1158/1535-7163.MCT-15-0712.