@article{f89ae97093e147b2940118c85738d2bf,
title = "Predictive Value of Combining Biomarkers for Clinical Outcomes in Advanced Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors",
abstract = "Introduction: A high tumor mutational burden (TMB) (≥10 mut/Mb) has been associated with improved clinical benefit in non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI) and is a tumor agnostic indication for pembrolizumab across tumor types. We explored whether combining TMB with programmed cell death ligand 1 (PD-L1) and pretreatment neutrophil-lymphocyte ratio (NLR) was associated with improved outcomes in ICI-treated NSCLC. Methods: We retrospectively analyzed patients treated with ICI with Foundation One genomic testing, including TMB. Optimal cutoff for prediction of response by TMB was determined by receiver operating characteristic analysis, and area under the curve (AUC) was calculated for all 3 biomarkers and combinations. Cox model was used to assess prognostic factors of overall survival (OS) and time to progression (TTP). Survival cutoffs calculated with Kaplan-Meier survival curves were TMB ≥10 mut/Mb, PD-L1 ≥50%, NLR <5, and combined biomarkers. Results: Data from 88 patients treated were analyzed. The optimal TMB cutoff was 9.24 mut/Mb (AUC, 0.62), improving to 0.74 combining all 3 biomarkers. Adjusted Cox model showed that TMB ≥10 mut/Mb was an independent factor of OS (hazard ratio [HR], 0.31; 95% confidence interval; 0.14-0.69; P = .004) and TTP (HR, 0.46; 95% CI, 0.27-0.77; P = .003). The combination of high TMB with positive PD-L1 and low NLR was significantly associated with OS (P = .038) but not TTP. Conclusions: TMB has modest predictive and prognostic power for clinical outcomes after ICI treatment. The combination of TMB, PD-L1, and NLR status improves this power.",
keywords = "Checkpoint blockade, Immunotherapy, Neutrophil lymphocyte ratio, PD-L1, TMB",
author = "Chester Kao and Eric Powers and Yuan Wu and Datto, {Michael B.} and Green, {Michelle F.} and Strickler, {John H.} and Ready, {Neal E.} and Tian Zhang and Clarke, {Jeffrey M.}",
note = "Funding Information: J.H. Strickler reports consulting/advisory board membership for Abbvie, Amgen, AstraZeneca, Bayer, Pfizer, Seattle Genetics, Viatris, Mereo Biopharma, and Natera; and research funding from Seattle Genetics, AstraZeneca, Daiichi-Sankyo, AStar D3, Genentech/Roche, OncoMed, Abbvie, Exelixis, Macrogenics, Leap Therapeutics, Sanofi, Amgen, and Nektar. Funding Information: N.E. Ready reports consulting/advisory board membership for Abbvie, Amgen, AstraZeneca, Bristol Myers Squibb, Pfizer, Genentech/Roche, Merck, G1 Therapeutics, Regeneron, and Jazz; and research funding from BMS and Merck. Funding Information: J.H. Strickler reports consulting/advisory board membership for Abbvie, Amgen, AstraZeneca, Bayer, Pfizer, Seattle Genetics, Viatris, Mereo Biopharma, and Natera; and research funding from Seattle Genetics, AstraZeneca, Daiichi-Sankyo, AStar D3, Genentech/Roche, OncoMed, Abbvie, Exelixis, Macrogenics, Leap Therapeutics, Sanofi, Amgen, and Nektar. T. Zhang reports consulting/advisory board membership for AstraZeneca, Bayer, Pfizer, Foundation Medicine, Janssen, Amgen, BMS, Calithera, Dendreon, and MJH Associates; consulting/speaking fees from Genomic Health and Sanofi Aventis; research funding (to Duke) from Pfizer, Janssen, Acerta, Abbvie, Novartis, Merrimack, OmniSeq, PGDx, Merck, Mirati, and Astellas; and stock ownership/employment (spouse) in Capio Biosciences, Archimmune Therapeutics, and Nanorobotics. N.E. Ready reports consulting/advisory board membership for Abbvie, Amgen, AstraZeneca, Bristol Myers Squibb, Pfizer, Genentech/Roche, Merck, G1 Therapeutics, Regeneron, and Jazz; and research funding from BMS and Merck. J.M. Clarke reports board of directors membership for the Lung Cancer Initiative of North Carolina (uncompensated); consulting/advisory board membership for AstraZeneca, Guardant, Merck, Eli Lily, Pfizer, NGM Biopharmaceuticals, and Spectrum; consulting/speaking for Merck and AstraZeneca; research/PI for Bristol-Myers Squibb, Eli Lily, Genentech, Spectrum, Adaptimmune, Medpacto, Bayer, AbbVie, Moderna, GlaxoSmithKline, Array, AstraZeneca, and Grid Therapeutics; and travel from Merck, AstraZeneca, Pfizer, and NGM Biopharmaceuticals. The remaining authors have stated that they have no conflicts of interest. Prior presentation: Presented at ASCO-SITC annual meeting 2020, Abstract #80. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
month = nov,
doi = "10.1016/j.cllc.2021.03.017",
language = "English (US)",
volume = "22",
pages = "500--509",
journal = "Clinical lung cancer",
issn = "1525-7304",
publisher = "Elsevier",
number = "6",
}