Comprehensive Genomic and Transcriptomic Analysis to Guide Therapy for Patients with Metastatic Solid Tumors

The added value of comprehensive genomic and transcriptomic profiling (CGTP) with whole-exome sequencing (WES) and whole-transcriptome sequencing (WTS) as compared with conventional targeted panel-based sequencing is not well-characterized for patients with cancer. We thus sought to determine the potential clinical utility of CGTP in a prospective clinical study in patients with advanced or metastatic solid tumors. We performed WES and WTS for patients who had prior targeted panel sequencing and had no DNA alterations with approved biomarker-matched therapies. We analyzed CGTP data of 99 patients with advanced cancers across 19 solid tumor types and assessed the presence of actionable DNA alterations and RNA expressions linked to approved or investigational agents. CGTP identified actionable genomic and transcriptomic alterations in 69.7% and 100% of cases, respectively. In this pilot study in which CGTP was incorporated into routine care, 19.2% of patients received biomarker-matched therapy. SIGNIFICANCE: This study demonstrates the feasibility and utility of extensive genomic and transcriptomic profiling to match patients with advanced cancer to molecularly informed treatments. Transcriptomic actionability analysis identifies actionable RNA expressions for patients beyond those with actionable DNA alterations, highlighting the potential of transcriptional profiling to enhance therapeutic opportunities in precision oncology.