AUTHOR=Huang Richard S. P. , Severson Eric , Haberberger James , Duncan Daniel L. , Hemmerich Amanda , Edgerly Claire , Ferguson N. Lynn , Frampton Garrett , Owens Clarence , Williams Erik , Elvin Julia , Vergilio Jo-Anne , Killian Jonathan Keith , Lin Douglas , Morley Samantha , McEwan Deborah , Holmes Oliver , Danziger Natalie , Cohen Michael B. , Sathyan Pratheesh , McGregor Kimberly , Reddy Prasanth , Venstrom Jeffrey , Anhorn Rachel , Alexander Brian , Brown Charlotte , Ross Jeffrey S. , Ramkissoon Shakti H. TITLE=Landscape of Biomarkers in Non-small Cell Lung Cancer Using Comprehensive Genomic Profiling and PD-L1 Immunohistochemistry JOURNAL=Pathology and Oncology Research VOLUME=27 YEAR=2021 URL=https://www.por-journal.com/journals/pathology-and-oncology-research/articles/10.3389/pore.2021.592997 DOI=10.3389/pore.2021.592997 ISSN=1532-2807 ABSTRACT=

Comprehensive genomic profiling (CGP) and immunohistochemistry (IHC) are important biomarker tools used for patients with non-small cell lung cancer (NSCLC) given the expanding number of standard-of-care therapies that require companion diagnostic testing. We examined 9450 NSCLC real-world patient samples that underwent both CGP and programmed death-ligand 1 (PD-L1) IHC to understand the biomarker landscape in this patient cohort. By assessing National Comprehensive Cancer Network (NCCN)-recommended biomarkers including genomic alterations, tumor mutational burden (≥10 mutations/Mb cut-off), and PD-L1 expression (Tumor Proportion Score (TPS) ≥ 50% cut-off), we show that CGP + PD-L1 IHC yielded potentially actionable results for 70.5% of the 9,450 patients with NSCLC. Among the remaining 29.5% (2,789/9,450) of patients, 86.7% (2,419/2,789) were potentially eligible for another biomarker-associated therapy and/or clinical trial based on their genomic profile. In addition, in the PD-L1TPS≥50% disease subset, BRAF mutations, MET mutations, MET amplifications, and KRAS mutations were significantly enriched; and in the PD-L1TPS<50%, EGFR mutations, ERBB2 mutations, STK11 mutations, and KEAP1 mutations were enriched. These findings highlight the improved clinical utility of combining CGP with IHC to expand the biomarker-guided therapeutic options available for patients with NSCLC, relative to single biomarker testing alone.