Monday, June 20, 2016

BRAF testing via blood rather than tumor tissue

BRAF Mutation Testing in Cell-Free DNA from the Plasma of Patients with Advanced Cancers Using a Rapid, Automated Molecular Diagnostics System.  Janku, Huang, Claes, Falchook, et al.  Mol Cancer Ther. 2016 May 20.

Cell-free (cf) DNA from plasma offers an easily obtainable material for BRAF mutation analysis for diagnostics and response monitoring. In this study, plasma-derived cfDNA samples from patients with progressing advanced cancers or malignant histiocytosis with known BRAF V600 status from formalin-fixed paraffin-embedded (FFPE) tumors were tested using a prototype version of the Idylla BRAF Mutation Test, a fully integrated real-time PCR-based test with turnaround time about 90 minutes. Of 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. Idylla had a sensitivity of 73% and specificity of 98%. A higher percentage, but not concentration, of BRAF V600 cfDNA in the wild-type background was associated with shorter overall survival and in patients with BRAF mutations in the tissue, who were receiving BRAF/MEK inhibitors, shorter time to treatment failure . Longitudinal monitoring demonstrated that decreasing levels of BRAF V600 cfDNA were associated with longer TTF . In conclusion, testing for BRAF V600 mutations in plasma cfDNA using the Idylla BRAF Mutation Test has acceptable concordance with standard testing of tumor tissue. A higher percentage of mutant BRAF V600 in cfDNA corresponded with shorter OS and in patients receiving BRAF/MEK inhibitors also with shorter TTF.

Quantitative assessment of BRAFV600 mutant circulating cell-free tumor DNA as a tool for therapeutic monitoring in metastatic melanoma patients treatd with BRAF/MEK inhibitors.  J Transl Med. 2016 Apr 19.  Schreuer, Meersseman, Van Den Herrewegen, et al.

BRAF V600 mutant circulating cell-free tumor DNA (BRAF V600mut ctDNA) could serve as a specific biomarker in patients with BRAF V600 mutant melanoma. We analyzed the value of BRAF V600mut ctDNA from plasma as a monitoring tool for advanced melanoma patients treated with BRAF/MEK inhibitors.

Allele-specific quantitative PCR analysis for BRAF V600 E/E2/D/K/R/M mutations was performed on DNA extracted from plasma of patients with known BRAF V600 mutant melanoma who were treated with dabrafenib and trametinib.

245 plasma samples from 36 patients were analyzed. In 16 patients the first plasma sample was obtained before the first dosing of dabrafenib/trametinib. At baseline, BRAF V600mut ctDNA was detected in 75 % of patients (n = 12/16). BRAF V600mut ctDNA decreased rapidly upon initiation of targeted therapy and became undetectable in 60 % of patients (n = 7/12) after 6 weeks of treatment. During treatment, disease progression (PD) was diagnosed in 27 of 36 patients. An increase of the BRAF V600mut ctDNA copy number and fraction, identified PD with a sensitivity of 70 % (n = 19/27) and a specificity of 100 %. An increase in the BRAF V600mut ctDNA fraction was detected prior to clinical PD in 44 % of cases (n = 12/27) and simultaneously with PD in 26 % of patients (n = 7/27).

Quantitative analysis of BRAF V600mut ctDNA in plasma has unique features as a monitoring tool during treatment with BRAF/MEK inhibitors. Its potential as an early predictor of acquired resistance deserves further evaluation.

The sensitivity and specificity numbers are pretty good here!  Plus, if we really could detect progression via a lab draw...earlier than we can with other assessments techniques....wouldn't that be awesome?  Patients...especially in the case of BRAFi could be placed on other therapies sooner...not to mention the earlier the heads-up in matter the treatment...the better!!

Prior posts regarding PCR testing: 
Nov 2015:  PCR testing for melanoma
Dec 2015:  Circulating tumor cells - how they may eventually impact melanoma diagnosis and response to therapy
Dec 2015:  PCR testing for circulating melanoma DNA - one more.... 
March 2016:  Biomarkers....  

Wishing you all my best - c

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