Landscape of Biomarkers in Non-small Cell Lung Cancer Using Comprehensive Genomic Profiling and PD-L1...

Area of Science:

• Oncology
• Genomics
• Pathology

Background:

• Biomarker testing is crucial for guiding non-small cell lung cancer (NSCLC) therapy.
• Expanding targeted therapies necessitate comprehensive companion diagnostic testing.

Purpose of the Study:

• To evaluate the biomarker landscape in a large cohort of NSCLC patients using both comprehensive genomic profiling (CGP) and programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC).
• To determine the actionable results and potential therapeutic eligibility when combining CGP with PD-L1 IHC in NSCLC.

Main Methods:

• Analysis of 9,450 real-world NSCLC patient samples subjected to both CGP and PD-L1 IHC.
• Assessment of NCCN-recommended biomarkers: genomic alterations, tumor mutational burden (TMB ≥10 mutations/Mb), and PD-L1 expression (Tumor Proportion Score (TPS) ≥50%).

Main Results:

• Combined CGP and PD-L1 IHC provided actionable results for 70.5% of NSCLC patients.
• Of the remaining patients, 86.7% showed potential eligibility for other biomarker-associated therapies or clinical trials based on genomic profiles.
• Specific mutations (e.g., BRAF, MET, KRAS) were enriched in PD-L1 high expressors, while others (e.g., EGFR, ERBB2, STK11, KEAP1) were enriched in PD-L1 low expressors.

Conclusions:

• Combining CGP with PD-L1 IHC significantly enhances the identification of biomarker-guided therapeutic options for NSCLC patients.
• This integrated approach offers greater clinical utility compared to single biomarker testing alone.
• The findings support the routine use of combined CGP and PD-L1 IHC for personalized NSCLC treatment strategies.