Liquid biopsy mutation panel for non-small cell lung cancer: analytical validation and clinical concordance

Abstract

Molecular testing for genomic variants is recommended in advanced non-small cell lung cancer (NSCLC). Standard tissue biopsy is sometimes infeasible, procedurally risky, or insufficient in tumor tissue quantity. We present the analytical validation and concordance study of EGFR variants using a new 17-gene liquid biopsy assay (NCT02762877). Of 144 patients enrolled with newly diagnosed or progressive stage IV nonsquamous NSCLC, 140 (97%) had liquid assay results, and 117 (81%) had both EGFR blood and tissue results. Alterations were detected in 58% of liquid samples. Overall tissue-liquid concordance for EGFR alterations was 94.0% (95% CI 88.1%, 97.6%) with positive percent agreement of 76.7% (57.7%, 90.1%) and negative percent agreement of 100% (95.8%, 100%). Concordance for ALK structural variants was 95.7% (90.1%, 98.6%). This assay detected alterations in other therapeutically relevant genes at a rate similar to tissue analysis. These results demonstrate the analytical and clinical validity of this 17-gene assay.

Capmatinib for patients with non-small cell lung cancer with MET exon 14 skipping mutations: A review of preclinical and clinical studies

“…Most patients with NSCLC are diagnosed with advanced metastatic disease [53]. Many of these patients may have tumors that are difficult to biopsy, are very small, and biopsies with minimal tumor content [54,55]. NGS allows detection of multiple gene alterations from a single sample, avoiding tissue exhaustion.…”

Liquid Biopsy for Advanced NSCLC: A Consensus Statement From the International Association for the Study of Lung Cancer

“…Since the first IASLC liquid biopsy statement, 11 additional literature supports extension of ctDNA analysis to all guideline-recommended and treatable oncogenic drivers, including ALK rearrangements, [70][71][72] ROS1 rearrangements, 71,73 BRAF mutations, 74 and, more recently, MET exon-14 skipping mutations, 75,76 RET rearrangements, 77 and HER2 mutations. 78 It is likely that the KRAS exon 2 p.G12C mutation will soon join this group. 79 Plasma NGS for ctDNA can detect both on-target (i.e., secondary mutations or amplification of the target gene) and off-target ("by-pass track") MOR, providing the exact status of tumor genotyping after disease progression to a targeted therapy and allowing a more rationale use of subsequent therapeutic lines.…”

The Emerging Therapeutic Landscape of ALK Inhibitors in Non-Small Cell Lung Cancer

“…Moreover, liquid biopsy is recommended in the College of American Pathologists (CAP)/International Association for the Study of Lung Cancer (IASLC)/Association for Molecular Pathology (AMP) guideline for the molecular testing of patients with NSCLC [ 80 ]. Various clinical studies have been conducted evaluating the concordance rate among plasma samples and tissue specimens [ 81 , 82 , 83 , 84 , 85 ]. The overall concordance rate for ALK fusion was reported at 95.7%, with a positive predictive value of 100% [ 83 ].…”

“…Various clinical studies have been conducted evaluating the concordance rate among plasma samples and tissue specimens [ 81 , 82 , 83 , 84 , 85 ]. The overall concordance rate for ALK fusion was reported at 95.7%, with a positive predictive value of 100% [ 83 ]. These recent findings are doubtless encouraging, yet some drawbacks should be improved before the liquid detection of molecular aberrations becomes a standard tool.…”