Use of Biomarkers in Individualization of Treatment

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Next-generation sequencing (NGS), also known as massively parallel sequencing (MPS), offers broad detection of genetic alterations that, in approximately one-third of patients with cancer, are “actionable,” meaning that they can be targeted by available therapeutics or the detection of the alteration can lead to a change in therapy. NGS is useful in the diagnosis of patients, determining their prognosis, appropriate treatment selection, and clinical trial enrollment. Many testing panels are available, each with different abilities to detect various mutation types. Clinicians not only have to decide which test to use, but which specimen to test, and when and how often to test. Aside from unique mutations, immunotherapy markers have become important for the use of checkpoint inhibitors, and their detection and interpretation can also be challenging. Efforts are underway to simplify and validate these assays. Meanwhile, clinicians should become educated about the benefit of, means of, and interpretation of genomic testing patients across the disease course.

Disclosures: Dr. Morrissette has disclosed that she has received consulting fees from Novartis Pharmaceuticals Corporation and BioRad.

Correspondence: Jennifer J.D. Morrissette, PhD, University of Pennsylvania, 3020 Market Street, Suite 220, Philadelphia, PA 19104. Email: jemorris@pennmedicine.upenn.edu
  • 1.

    Association for Molecular Pathology Training and Education Committee. ONCOLOGY: Interpretation of Genomic Assays. Revised October 2019. Accessed July 5, 2020. Available at: https://www.amp.org/AMP/assets/File/education/MIMP/NGSInterpretation_10_8_19.pdf?pass=15

  • 2.

    Zehir A, Benayed R, Shah RH, Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients [published correction appears in Nat Med 2017;23:1004]. Nat Med 2017;23:703713.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3.

    Zill OA, Banks KC, Fairclough SR, The landscape of actionable genomic alterations in cell-free circulating tumor DNA from 21,807 advanced cancer patients. Clin Can Res 2018;24:35283538.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Zhang Y, Chang L, Yang Y, Intratumor heterogeneity comparison among different subtypes of non-small-cell lung cancer through multi-region tissue and matched ctDNA sequencing. Mol Cancer 2019;18:7.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Aggarwal C, Thompson JC, Black TA, Clinical implications of plasma-based genotyping with the delivery of personalized therapy in metastatic non-small cell lung cancer. JAMA Oncol 2019;5:173180.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Mittmann N, Earle CC, Cheng SY, Population-based study to determine the health system costs of using the 21-gene assay. J Clin Oncol 2018;36:238243.

  • 7.

    Chalmers ZR, Connelly CF, Fabrizio D, Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Medicine 2017;9:34.

  • 8.

    Buchhalter I, Rempel E, Endris V, Size matters: dissecting key parameters for panel-based tumor mutational burden analysis. Int J Cancer 2019;144:848858.

  • 9.

    US Food & Drug Administration. FDA approves pembrolizumab for adults and children with TMB-H solid tumors. Accessed June 5, 2020. Available at: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-pembrolizumab-adults-and-children-tmb-h-solid-tumors.

  • 10.

    Aggarwal C, Thompson JC, Chien AL, Baseline plasma tumor mutation burden predicts response to pembrolizumab-based therapy in patients with metastatic non-small cell lung cancer. Clin Cancer Res 2020;26:23542361.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
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