Twenty-five years with companion diagnostics.

For decades, pharmacotherapy has been hampered by significant patient variability, and the inability to predict outcomes at the individual patient level has negatively affected its value. However, progress in molecular medicine has led to an increased understanding of the pathophysiology and mechanisms of action of drugs, thereby enabling the development of predictive biomarkers. Companion diagnostics (CDx) belongs to the group of predictive biomarkers, which the Food and Drug Administration (FDA) defines as an in vitro diagnostic device that provides information that is essential for the safe and effective use of a corresponding therapeutic product. In September 1998, 25 years ago, the FDA approved the first CDx assay, the HercepTest, an immunohistochemical (IHC) assay for the detection of HER2 protein expression. This assay is linked to the use of the monoclonal antibody trastuzumab in the treatment of HER2 positive breast cancer. The HercepTest is not the only CDx developed. Currently, more than 60 drugs or drug combinations, primarily in hematology and oncology, have been approved by the FDA, with CDx assays linked to their use. The current article briefly discusses the subject of CDx and provides an overview of its evolution over the past 25 years, with particular emphasis on the United States.