The Evolution of Oncology Companion Diagnostics from Signal Transduction to Immuno-Oncology
Cet article analyse l'évolution des tests compagnons en oncologie ainsi que les difficultés liées à leur développement à l'ère des thérapies ciblées et de l'immunothérapie
Sixteen oncology drugs have been approved with a companion diagnostic (CDx) test by the FDA. These represent only 9.6% of the 167 oncology drug approvals since 1998, the year the first CDx test for Herceptin was approved. The great majority of CDx tests are for drugs that inhibit signal transduction pathways by either inhibiting the intracellular kinase activity with a small molecule or preventing ligand-induced receptor activation with a monoclonal antibody. In most of these cases, prospective patient selection for the biomarker-positive subpopulation was initiated in or before Phase II. The development of CDx tests for emerging immunotherapies will be more complicated because they are not dependent on driver mutations in the drug target, the mechanism of action is often pleiotropic, and will require both protein and cell-based assays to evaluate the interaction of the tumor with the immune system. Consequently, we will need to develop new biomarker strategies for the development of immunotherapies and to determine whether the optimum strategy is to release a prior checkpoint blockade in patients with a suppressed immune response, or to prime a new immune response to the tumor.
Trends
A small minority of oncology drugs have been approved with a companion diagnostic (CDx) test by the US Food and Drug Administration.
CDx tests measure the status of drug target (usually a driver mutation) using single analyte tests on standard assay platforms.
Clinical utility is based on a large difference in drug response between CoDx-defined subgroups.
Development of CDx for emerging immunotherapies will be more complicated because they are not dependent on driver mutations in the drug target.
Trends in Pharmacological Sciences , résumé, 2015