Integration of Biomarker Validation in Clinical Development in Oncology
The development and qualification of biomarkers are keys to the future of drug development and precision medicine, particularly in oncology.
Read IDDI Article published in Applied Clinical Trials.
Precision medicine relies on validated biomarkers that allow classification of patients by their probable disease risk, prognosis, or response to treatment.1 Diagnostic biomarkers identify patients who are eligible for a given treatment due to the presence of a molecular alteration, such as mutation or gene rearrangement. A prognostic biomarker is used to identify the likelihood of a clinical event, such as disease recurrence or death. More relevant to precision medicine, predictive biomarkers distinguish patients who are likely to benefit from a given treatment, or conversely, to benefit from alternative treatments. A topical example in oncology is the presence of activating mutations of the epidermal growth factor receptor (EGFR); such mutations are associated with benefit from treatment with tyrosine-kinase inhibitors in non-small-cell lung cancer (NSCLC).2 Importantly, establishing that a biomarker is predictive generally requires a comparison against control treatment in individuals with and without the biomarker, usually in randomized trials.1
The development and qualification of biomarkers are keys to the future of drug development and precision medicine, particularly in oncology. A validated predictive biomarker may become a companion diagnostic (CDx), defined by the Food and Drug Administration (FDA) as a medical device, often an in-vitro diagnostic device (IVD), which provides information that is essential for the safe and effective use of a corresponding drug or biological product.3 Moreover, integrating biomarkers into the therapeutic development process may allow less promising projects to be stopped earlier (especially before they enter into costly phase 3 trials), thus optimizing the total cost of drug development.