Real-world clinical utility of comprehensive genomic profiling in advanced solid tumors

Area of Science:

• Oncology
• Genomics
• Precision Medicine

Background:

• Comprehensive genomic profiling (CGP) is essential in precision oncology.
• Its real-world utility and impact on patient outcomes require further investigation.
• Large-scale analysis is needed to understand variations across diverse tumor types.

Purpose of the Study:

• To evaluate the real-world utility of CGP in a large cohort of advanced solid tumor patients in Japan.
• To assess the prognostic value of CGP-guided clinical evidence-level classification.
• To identify inter-tumor type differences in CGP benefit and explore tumor-agnostic biomarkers.

Main Methods:

• Analysis of clinical and genetic data from 54,185 advanced solid tumor patients who underwent CGP.
• Utilized a targeted sequencing panel covering 324 genes.
• Assessed CGP-guided therapies, clinical evidence levels, and prognostic associations.

Main Results:

• Actionable alterations predicting response to approved therapies were found in 16.6% of patients.
• CGP-guided therapies were administered to 8% of patients, with improvement over time.
• Significant variations in CGP utility were observed across tumor types, e.g., >20% in thyroid/lung vs. <2% in pancreatic/liver cancers.
• Tumor mutational burden (TMB) ≥20 mutations/megabase predicted better outcomes with pembrolizumab across tumor types.

Conclusions:

• CGP provides valuable real-world insights for individualized cancer treatment.
• Clinical utility and benefit of CGP vary significantly by tumor type.
• Tumor-agnostic biomarkers like TMB show promise in guiding immunotherapy decisions.