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. 2021 Mar 11:27:592997.
doi: 10.3389/pore.2021.592997. eCollection 2021.

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

Richard S P Huang  1 , Eric Severson  1 , James Haberberger  1 , Daniel L Duncan  1 , Amanda Hemmerich  1 , Claire Edgerly  1 , N Lynn Ferguson  1 , Garrett Frampton  2 , Clarence Owens  1 , Erik Williams  2 , Julia Elvin  2 , Jo-Anne Vergilio  2 , Jonathan Keith Killian  2 , Douglas Lin  2 , Samantha Morley  2 , Deborah McEwan  2 , Oliver Holmes  2 , Natalie Danziger  2 , Michael B Cohen  3   4 , Pratheesh Sathyan  2 , Kimberly McGregor  2 , Prasanth Reddy  2 , Jeffrey Venstrom  2 , Rachel Anhorn  2 , Brian Alexander  2 , Charlotte Brown  1 , Jeffrey S Ross  1   5 , Shakti H Ramkissoon  1   3   4
Affiliations

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

Richard S P Huang et al. Pathol Oncol Res. .

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.

Keywords: PD-L1; biomarkers; comprehensive genomic profiling; immunohistochemistry; non-small cell lung cancer.

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Conflict of interest statement

Authors RH, ES, JH, DD, AH, CE, NF, CO, CB, JR, SR, GF, EW, JE, JV, JK, DL, SM, DM, OH, ND, PS, KM, PR, JV, RA, and BA were employed by the company Foundation Medicine, Inc., which is a wholly subsidiary of Roche and receive stock from Roche. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Patients with non-small cell lung cancer (NSCLC) eligible for therapy based on biomarker status. By assessing genomic driver alterations, tumor mutational burden (≥10 mutations/Mb cut-off), and PD-L1 expression (TPS ≥ 50% cut-off), we show that CGP + PD-L1 IHC yielded potentially actionable results, per National Comprehensive Cancer Network (NCCN) guidelines, 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 total, combined CGP and PD-L1 IHC testing provided positive biomarker statuses for 96.1% of 9,450 patients with NSCLC when considering potential eligibility for biomarker associated therapies and clinical trial enrollment.
FIGURE 2
FIGURE 2
Percent of negative, low positive, and high positive PD-L1 cases of NSCLC subtypes. An increased high positive rate was detected in sarcomatoid carcinoma subtype vs. adenocarcinoma subtype (p = 0.025, t-test) and in large cell carcinoma subtype vs. adenocarcinoma subtype (p = 0.025, t-test).
FIGURE 3
FIGURE 3
Relationship between PD-L1 and tumor mutational burden in NSCLC using a PD-L1 TPS ≥ 50% cut-off and a TMB ≥ 10 mutations/Mb cut-off.
See this image and copyright information in PMC

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