Use of Companion Diagnostics (CDx) and Predictive Biomarkers for Cancer Targeted Therapy: Clinical Applications in Precision Medicine

  • Rosanne WelcherEmail author


In the field of oncology therapeutics, biomarker assays play an increasingly important role from discovery research to patient management. Companion Diagnostic (CDx) assays play an important role in precision medicine, having a specific clinical utility to aid in the identification of patients eligible to receive a therapeutic treatment, or to predict which patients may respnd to a targeted therapy. CDx assays may also affect the design of clinical trials, which can lead to higher patient response rates when the right patients are selected for treatment. CDx assays can also accelerate the introduction of new therapeutics, enabling a smaller number of patients to be enrolled in studies, reducing the number of patients exposed to investigational or approved therapeutics, thereby decreasing the chance of side effects. With the introduction of immuno-oncology drugs such as anti-PD-L1 and anti-PD-1 therapeutics, biomarker assays have become even more critically important in understanding the interactions between the tumor cells and immune response, and predicting patient responses. This chapter will review the history of CDx and present a high-level overview of the development path of CDx. It will also provide a survey of current FDA-approved or FDA-cleared CDx assays, examine some of the challenges in CDx development, and explore technologies and assay types applicable to CDx important in the next generation of oncology therapeutics.


Companion diagnostics Predictive biomarkers Immuno-oncology Cancer targeted therapy FDA Complementary diagnostics Laboratory-developed tests 


  1. 1.
    Romond EH, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353:1673–84.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Ménard, et al. HER2 as a prognostic factor in breast cancer. Oncology. 2001;61(Suppl 2):67–72.CrossRefPubMedGoogle Scholar
  3. 3.
    Vogel CL, Cobleigh MA, Tripathy D, Gutheil JC, Harris LN, Fehrenbacher L, et al. First-line Herceptin monotherapy in metastatic breast cancer. Oncology. 2001;61(Suppl 2):37–42.CrossRefPubMedGoogle Scholar
  4. 4.
    Baselga J. Clinical trials of Herceptin(trastuzumab). Eur J Cancer. 2001;37(Suppl 1):S18–2.CrossRefPubMedGoogle Scholar
  5. 5.
    Lee JW, Devanarayan V, Barrett YC, et al. Fit-for-purpose method development and validation for successful biomarker measurement. Pharm Res. 2006;23(2):312–28.CrossRefPubMedGoogle Scholar
  6. 6.
    Olsen D, Jorgensen JT. Companion diagnostics for targeted cancer drugs – clinical and regulatory aspects. Front Oncol. 2014;4:105.CrossRefPubMedCentralPubMedGoogle Scholar
  7. 7.
    Audette J. FDA introduces a new test concept: “complementary diagnostics”. Amplion; 2015.Google Scholar
  8. 8.
    Novotny JF Jr, Cogswell J, Inzunza H, et al. Establishing a complementary diagnostic for anti-PD-1 immune checkpoint inhibitor therapy. Ann Oncol. 2016;27(10):1966–9.CrossRefPubMedCentralPubMedGoogle Scholar
  9. 9.
    Meijuan L. Statistical methods for clinical validation of follow-on companion diagnostic devices via an external concordance study. Stat Biopharma Res. 2016;8(3):355–63.CrossRefGoogle Scholar
  10. 10.
    Hirsch FR, et al. PD-L1 immunohistochemistry assays for lung cancer: results from phase 1 of the blueprint PD-L1 IHC Assay Comparison Project. J Thorac Oncol. 2016;12(2):208–22.CrossRefPubMedCentralPubMedGoogle Scholar
  11. 11.
    U.S. Department of Health and Human Services, Food and Drug Administration, Center for Devices and Radiological Health, Center for Biologics Evaluation and Research, Center for Drug Evaluation and Research. In vitro companion diagnostic devices: guidance for industry and food and drug administration staff. 2014.Google Scholar
  12. 12.
    U.S. Department of Health and Human Services, Food and Drug Administration, Center for Devices and Radiological Health, Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research. Principles for codevelopment of an in vitro companion diagnostic device with a therapeutic product: draft guidance for industry and food and drug administration staff. 2016.Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Companion DiagnosticsAgilent TechnologiesCarpinteriaUSA

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