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IMMUNOTHERAPY

TMB — a histology-agnostic predictor of the efficacy of ICIs?

Nature Reviews Clinical Oncology volume 17, page 718 (2020)Cite this article

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Tumour mutational burden (TMB) is hypothesized to correlate with the neoantigen load and thus the immunogenicity of tumours. Indeed, data from retrospective studies suggest that cancers with a high TMB are more likely to respond to immune-checkpoint inhibitors (ICIs). Now, the predictive value of TMB across diverse cancers has been investigated in a prospectively planned retrospective biomarker analysis of the KEYNOTE-158 study.

KEYNOTE-158 is a multicohort, nonrandomized phase II study designed to test the efficacy of the ICI pembrolizumab, an anti-PD-1 antibody, in adult patients with ten different types of treatment-refractory, advanced-stage solid tumours: anal, biliary, cervical, endometrial, neuroendocrine, salivary, small-cell lung, thyroid or vulvar cancer or mesothelioma. TMB was determined in tumour specimens using the FoundationOne CDx assay. Among 790 patients evaluable for TMB and efficacy, 102 (13%) had TMB-high (TMB-H) tumours according to a threshold of ≥10 mutations per Mb.

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  1. Nature Reviews Clinical Oncology http://www.nature.com/nrclinonc

    David Killock

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  1. David Killock
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Correspondence to David Killock.

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Killock, D. TMB — a histology-agnostic predictor of the efficacy of ICIs?. Nat Rev Clin Oncol 17, 718 (2020). https://doi.org/10.1038/s41571-020-00438-0

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