@inbook{a4382cbfed9c4fcbb9674e32e56e70c8,
title = "Biomarkers: Is Tumor Mutational Burden the New Prognostic Grail?",
abstract = "Immune checkpoint inhibitors (ICI) have improved outcomes for patients with advanced non-small cell lung cancer (NSCLC). However, only a minority of patients experience benefit, and biomarkers of response are needed to improve patient selection. Tumor mutational burden (TMB), defined as the number of somatic mutations in a tumor, has been identified as a potential predictive biomarker. Studies assessing TMB and outcome in NSCLC have demonstrated improved response rates and progression-free survival to ICIs in patients with higher TMB compared to lower TMB, and patients with high TMB have a higher likelihood of benefit to ICI compared to chemotherapy. However, TMB imperfectly stratifies responders from non-responders, and these data are heterogenous with respect to treatment context, drug, TMB assay, and TMB threshold. Importantly, many of these analyses are retrospective, and few prospective clinical trials implementing TMB as a biomarker have been completed. Additional limitations to the implementation of TMB include the need for adequate tissue to perform sequencing, and heterogeneity in TMB assays. Efforts to develop blood-based TMB assays and standardization procedures may help address these limitations. Finally, further research to understand why TMB associates with response, and how TMB interacts with other biomarkers including PD-L1 and interferon-gamma expression, may help improve its predictive power.",
keywords = "Biomarker, CTLA-4, Immune checkpoint inhibitor, Immunotherapy, Neoantigen, PD-1, PD-L1, Tumor mutational burden",
author = "Vokes, {Natalie I.} and Awad, {Mark M.}",
note = "Publisher Copyright: {\textcopyright} 2021, Springer Nature Switzerland AG.",
year = "2021",
doi = "10.1007/978-3-030-74028-3_2",
language = "English (US)",
series = "Current Cancer Research",
publisher = "Springer Nature",
pages = "27--54",
booktitle = "Current Cancer Research",
address = "United States",
}