Comparison of whole-exome, whole-transcriptome genomic profiling and targeted sequencing with 50-gene panels in advanced solid tumors

Abstract

There are a growing number of options for therapies matched to molecular biomarkers in solid tumors. This study evaluated the value of genomic profiling in advanced solid tumors using whole-exome, whole-transcriptome sequencing (WES/WTS) in comparison to 50-gene panels. We retrospectively reviewed clinical reports from tumor samples tested with a WES/WTS assay to determine the proportion of samples across 11 tumor types that would have had a matched therapy identified using each of four 50-gene panels and performed these analyses across different classifications of biomarker actionability. We found that, depending on the panel, between 4.2% and 9.1% of the 6943 samples had at least one alteration associated with an on-label FDA-approved therapy identified by WES/WTS but no such alteration identified by the 50-gene panel. Most had high tumor mutational burden (TMB) and/or high microsatellite instability (MSI), or homologous recombination repair (HRR) gene alterations. When considering other opportunities for matched therapy, up to 17.7% of samples had potentially actionable alterations identified by WES/WTS but none identified by the 50-gene panel. This increased to as high as 32.6% when we included alterations associated with clinical trials. Our findings highlight the value of comprehensive WES/WTS-based genomic profiling to identify potential matched therapies, thereby informing clinical decision-making and potentially improving outcomes for more patients.