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Predictive Biomarkers and Targeted Therapies in Immuno-oncology

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Predictive Biomarkers in Oncology

Abstract

Cancer immunotherapy (CIT) has transformed our approach in diagnosis and treatment of cancer. However, durable responses or cures are only seen in a minority of patients, illustrating the need for reliable biomarkers that identify patients most likely to receive meaningful clinical benefit. PD-L1 immunohistochemistry (IHC) has been extensively used in clinical development programs for anti-PD-L1/PD-1 targeted therapies. Notably, four independently developed PD-L1 IHC assays have demonstrated clinically meaningful predictive value in several indications and are approved as companion or complementary diagnostics. PD-L1 IHC is by no means a flawless biomarker or diagnostic. Numerous studies have found that a subset of PD-L1 negative patients do in fact derive clinical benefit from CIT therapy, highlighting the need for more precise diagnostic tools. Gene signatures with emphasis on immune-related biology and tumor mutation burden, a surrogate for neoantigen presentation, have both emerged as new promising CIT biomarkers and have demonstrated predictive value in exploratory clinical studies. As of today, neither of these biomarkers has gained approval as a companion or complementary diagnostic or has shown the capacity to accurately capture all patients that could potentially benefit from CIT. It is likely, based on the complexity of the tumor microenvironment, that more than one biomarker will be required to identify patients that benefit from CIT in the future.

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Author information

Authors and Affiliations

  1. Research Pathology, Genentech, South San Francisco, CA, USA

    Hartmut Koeppen

  2. Department of Oncology Biomarker Development, Genentech, South San Francisco, CA, USA

    Mark L. McCleland & Marcin Kowanetz

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  1. Hartmut Koeppen
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  2. Mark L. McCleland
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  3. Marcin Kowanetz
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Correspondence to Hartmut Koeppen .

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Editors and Affiliations

  1. Department of Pathology and Lab Medicine, Indiana University School of Medicine, Indianapolis, IN, USA

    Sunil Badve

  2. Targos Inc., Issaquah, WA, USA

    George Louis Kumar

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Koeppen, H., McCleland, M.L., Kowanetz, M. (2019). Predictive Biomarkers and Targeted Therapies in Immuno-oncology. In: Badve, S., Kumar, G. (eds) Predictive Biomarkers in Oncology. Springer, Cham. https://doi.org/10.1007/978-3-319-95228-4_29

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  • DOI: https://doi.org/10.1007/978-3-319-95228-4_29

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