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

Area of Science:

• Oncology
• Genomics
• Molecular Diagnostics

Background:

• The clinical utility of comprehensive genomic and transcriptomic profiling (CGTP) compared to targeted panels is not well-defined for cancer patients.
• Advanced or metastatic solid tumors often lack actionable targets identified by conventional sequencing methods.

Purpose of the Study:

• To prospectively evaluate the clinical utility of CGTP, integrating whole exome sequencing (WES) and whole transcriptome sequencing (WTS).
• To assess the identification of actionable genomic and transcriptomic alterations in patients with advanced cancers who had prior negative targeted panel sequencing.

Main Methods:

• Prospective clinical study involving 99 patients with advanced solid tumors across 19 types.
• Performed WES and WTS on patients with prior targeted panel sequencing and no identified biomarker-matched therapies.
• Analyzed CGTP data for actionable DNA alterations and RNA expressions linked to approved or investigational agents.

Main Results:

• CGTP identified actionable genomic alterations in 69.7% of patients.
• Actionable transcriptomic alterations were identified in 100% of patients.
• 19.2% of patients received biomarker-matched therapy in this pilot study integrating CGTP into routine care.

Conclusions:

• CGTP demonstrates significant potential clinical utility in advanced cancer patients, revealing actionable targets missed by targeted panels.
• Integrating WES and WTS provides a comprehensive molecular profile, increasing opportunities for biomarker-matched therapies.
• Further studies are warranted to confirm the impact of CGTP on patient outcomes in routine clinical practice.