Evaluation and comparison of two commercially available targeted next-generation sequencing platforms to assist oncology decision making

Abstract

BackgroundIt is widely acknowledged that there is value in examining cancers for genomic aberrations via next-generation sequencing (NGS). How commercially available NGS platforms compare with each other, and the clinical utility of the reported actionable results, are not well known. During the course of the current study, the Foundation One (F1) test generated data on a combination of somatic mutations, insertion and deletion polymorphisms, chromosomal abnormalities, and deoxyribonucleic acid (DNA) copy number changes at ~250× coverage, while the Paradigm Cancer Diagnostic (PCDx) test generated the same type of data at >5,000× coverage, plus provided messenger RNA (mRNA) expression levels. We sought to compare and evaluate paired formalin-fixed paraffin-embedded tumor tissue using these two platforms.MethodsSamples from patients with advanced solid tumors were submitted to both the F1 and PCDx vendors for NGS analysis. Turnaround time (TAT) was calculated. Biomarkers were considered clinically actionable if they had a published association with treatment response in humans and were assigned to the following categories: commercially available drug (CA), clinical trial drug (CT), or neither option (hereafter referred to as “None”).ResultsThe demographics of the 21 unique patient tumor samples included ten men and eleven women, with a median age of 56 years. Due to insufficient archival tissue from the same collection period, in one case, we used samples from different collections. PCDx reported first results faster than F1 in 20 cases. When received at both vendors on the same day, PCDx reported first results for 14 of 15 cases, with a median TAT of 9 days earlier than F1 (P<0.0001). Categorization of CA compared to CT and none significantly favored PCDx (P=0.012).ConclusionIn the current analysis, commercially available NGS platforms provided clinically relevant actionable targets (CA or CT) in 47%–67% of diverse cancer types. In the samples analyzed, PCDx significantly outperformed F1 in TAT, and had statistically significant higher clinically relevant actionable targets categorized as CA.

Clinicopathologic Features of Non–Small-Cell Lung Cancer Harboring an NTRK Gene Fusion

“…Assays utilized identified fusions using variety of technologies as follows: RNA-based fusion targeted Anchored Multiplex PCR and Illumina sequencing 10 (Massachusetts General Hospital (MGH) Solid Fusion Assay, Memorial Sloan Kettering (MSK) Solid Fusion Assay, ArcherDx FusionPlex performed at Caris Life Sciences); DNA hybridization capture with intron tiling and Illumina sequencing (Foundation One 11 , MSK IMPACT 12,13 ); total nucleic acid extraction, PCR amplification, and Ion Torrent Sequencing (Paradigm PCDx 14 ).…”

Tumor Cell–Free DNA Copy Number Instability Predicts Therapeutic Response to Immunotherapy

“…Genomic testing of representative tumor biopsies provides mutational status of known driver genes, but methods currently available are reported to be inconsistent (5)(6)(7). Sequential biopsies during therapy have been proposed to capture alterations in driver mutations occurring with selection pressures from systemic therapies (8), which is often contraindicated due to technical or safety issues and patient reluctance.…”

“…Sequential biopsies during therapy have been proposed to capture alterations in driver mutations occurring with selection pressures from systemic therapies (8), which is often contraindicated due to technical or safety issues and patient reluctance. As an alternative, "liquid biopsies," utilizing tumorderived cell-free DNA (cfDNA) present in plasma can be used (9) as a minimally invasive method to identify "actionable" mutations with their inherent limitations, for example, frequencies of such mutations being only 50% or lower (10), and conflicting results by technology (6,7).…”

Comparing two assays for clinical genomic profiling: the devil is in the data

“…We read with concern the paper “Evaluation and comparison of two commercially available targeted next-generation sequencing platforms to assist oncology decision-making”. 1 The study directly compared results for the Paradigm Cancer Diagnostic test to the FoundationOne test for formalin-fixed, paraffin-embedded specimen pairs from 21 advanced cancer cases. We believe this study is fundamentally flawed, misleading, and potentially dangerous for patient care, for the reasons outlined herein.…”