Liquid Biopsy Test Detects Non-Small-Cell Lung Cancer

Plasma-based assays overcome key challenges associated with tissue-based approaches, enabling sensitive, accurate, real-time mutation detection in non-small-cell lung cancer patients.

New clinical performance data has demonstrated high sensitivity and specificity of the novel exosome-based liquid biopsy test in patients with non-small-cell lung cancer (NSCLC) suspected to be positive for echinoderm microtubule-associated protein-like 4 (EML4) gene fused to the anaplastic lymphoma kinase (ALK) gene, known as EML4-ALK translocations.

The new data shows the ability of proprietary exosomal ribonucleic acid (exoRNA) plus cell-free DNA (cfDNA) platform to detect with high sensitivity epidermal growth factor receptor (EGFR) activating mutations and the EGFR T790M resistance mutation in blood plasma of patients with NSCLC. The test demonstrated the ability to determine the variant-specific expression profile of EML4-ALK fusion transcripts in plasma samples from 24 NSCLC patients with known ALK tissue status by fluorescence in situ hybridization (FISH). Specifically, the test demonstrated 88% sensitivity and 100% specificity, with the ability to differentiate between v1, v2, v3a,b,c fusion-specific transcripts. These represent the vast majority of all EML4-ALK-positive cases.

In the study, Exosome Diagnostics, Inc., (Cambridge, MA, USA) used its ExoDx Solid Tumor mutation detection panel, which extracts exoRNA and captures cfDNA in a single step, to analyze 47 blood plasma samples from NSCLC patients collected at the time of clinical resistance to EGFR tyrosine kinase inhibitor (TKI) therapy. The samples were EGFR-genotyped on time-matched tissue from a repeat biopsy. The exoRNA and cfDNA were then simultaneously analyzed utilizing targeted ultra-deep sequencing (UDS) of select genes.

The positive concordance of EGFR mutations in metastatic disease was 86.0% for the activating mutations EGFR L858R and del19, and 64.7% for the resistance EGFR T790M mutation. In patients with intrathoracic disease (M0/M1a), these mutations have proven challenging to detect utilizing cfDNA alone. However, by combining exoRNA and cfDNA, Exosome Diagnostics achieved a 72.7% concordance for activating EGFR mutations.

Vincent J. O'Neill, MD, MRCP, Chief Medical Officer at Exosome Diagnostics, said, “We're extremely pleased with these new data and the strong clinical performance of ExoDx Lung(ALK), The ability to detect specific fusion transcripts of the ALK gene represents a critical advance in the detection of this mutation. With the test, we believe we will be able to give physicians the most complete molecular information they need in order to direct patients to the most targeted and appropriate available treatment or clinical trial.” The study was presented at the 16th World Conference on Lung Cancer held September 6–9, 2015, in Denver (CO, USA) .

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Exosome Diagnostics, Inc.