Landscape of Biomarkers in Non-small Cell Lung Cancer Using Comprehensive Genomic Profiling and PD-L1 Immunohistochemistry
Richard S.P. Huang, Eric A. Severson, James Haberberger, Daniel Duncan, Amanda Hemmerich, Claire Edgerly, N. Lynn Ferguson, Garrett M. Frampton, Clarence Owens, Erik A. Williams, Julia A. Elvin, Jo‐Anne Vergilio, Jonathan Keith Killian, Douglas I. Lin, Samantha Morley, Deborah McEwan, Oliver Holmes, Natalie Danziger, Michael B. Cohen, Pratheesh Sathyan, Kimberly McGregor, Prasanth Reddy, Jeffrey M. Venstrom, Rachel Anhorn, Brian M. Alexander, Charlotte A. Brown, Jeffrey S. Ross, Shakti Ramkissoon
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-L1 TPS≥50% disease subset, BRAF mutations, MET mutations, MET amplifications, and KRAS mutations were significantly enriched; and in the PD-L1 TPS<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.