StrandAdvantage test for early‐line and advanced‐stage treatment decisions in solid tumors

Abstract

Comprehensive genetic profiling of tumors using next‐generation sequencing (NGS) is gaining acceptance for guiding treatment decisions in cancer care. We designed a cancer profiling test combining both deep sequencing and immunohistochemistry (IHC) of relevant cancer targets to aid therapy choices in both standard‐of‐care (SOC) and advanced‐stage treatments for solid tumors. The SOC report is provided in a short turnaround time for four tumors, namely lung, breast, colon, and melanoma, followed by an investigational report. For other tumor types, an investigational report is provided. The NGS assay reports single‐nucleotide variants (SNVs), copy number variations (CNVs), and translocations in 152 cancer‐related genes. The tissue‐specific IHC tests include routine and less common markers associated with drugs used in SOC settings. We describe the standardization, validation, and clinical utility of the StrandAdvantage test (SA test) using more than 250 solid tumor formalin‐fixed paraffin‐embedded (FFPE) samples and control cell line samples. The NGS test showed high reproducibility and accuracy of >99%. The test provided relevant clinical information for SOC treatment as well as more information related to investigational options and clinical trials for >95% of advanced‐stage patients. In conclusion, the SA test comprising a robust and accurate NGS assay combined with clinically relevant IHC tests can detect somatic changes of clinical significance for strategic cancer management in all the stages.

Identifying a Clinically Applicable Mutational Burden Threshold as a Potential Biomarker of Response to Immune Checkpoint Therapy in Solid Tumors

“…To test whether assays that interrogate a fraction of the exome can identify iCAM+ tumors, the mutational burden of TCGA tumors was recomputed by restricting the data to genomic regions assayed by two commercial assays: FoundationOne 6 (315/236 genes, http://foundationone.com) and StrandAdvantage 15 (selected regions of 152 genes, https://www.strandcenters.com/strand-advantage/). ROC curves (Figure 3) for iCAM+ versus iCAM− class prediction of tumors from TCGA using mutations sequenced by these assays (Data Supplement) showed that FoundationOne 6 (AUC: 0.85-0.99) and StrandAdvantage 15 (AUC: 0.78-0.98) can identify iCAM+ tumors accurately.…”

“…ROC curves (Figure 3) for iCAM+ versus iCAM− class prediction of tumors from TCGA using mutations sequenced by these assays (Data Supplement) showed that FoundationOne 6 (AUC: 0.85-0.99) and StrandAdvantage 15 (AUC: 0.78-0.98) can identify iCAM+ tumors accurately.…”

“…Applied to an independent melanoma dataset using the FoundationOne assay 6 , iCAM+ status was able to identify responders to single-agent PD-1 blockade with high accuracy. Although FoundationOne 6 and StrandAdvantage 15 assays were used here, any hybrid-capture-based assay that identifies mutations in a substantial portion of the exome could be used. Note that these assays do not have germline controls, so some variant calls may be rare germline polymorphisms.…”

“…Receiver operating characteristic curves for iCAM status determination of The Cancer Genome Atlas (TCGA) samples using only the exons used in FoundationOne 6 (orange) and StrandAdvantage 15 (green) assays. WXS TCGA classification was used as the gold standard.…”

Analysis of solid tumor mutation profiles in liquid biopsy

“…Two hundred nanograms was used as input for the SA152 panel while 20‐40 ng was used for the Swift panel. Somatic variants were identified and prioritized using Strand's proprietary tools, Strand NGS (http://www.strand-ngs.com), and StrandOMS (previously StrandOmics), respectively . Sixty‐four lung cancer samples were tested for EGFR mutations on cobas EGFR Mutation Test v2 (Roche Molecular Systems, Inc, CA, USA) at source.…”