Are Companion Diagnostics Useful?

Abstract

We define a companion diagnostics (CDx)5 test as any diagnostic tool that guides the selection of patient treatment. In the US, these tests include diagnostics cleared by the Food and Drug Administration (FDA), as well as laboratory-developed tests (LDTs) run in CLIA-accredited laboratories. The answer to the title's question is obviously in the affirmative. We discuss the growing need to improve, accelerate, and standardize oncology CDx that benefit patients. Recent advances in our understanding of the mutational landscape of cancers have led to the rapid development of targeted therapies for pathogenomic targets. At the same time, advances in next-generation sequencing (NGS) have revealed the complexity of heterogeneous cancers. With the fast pace of change occurring in clinical oncology, flexible approaches to CDx development are needed while test accuracy is maintained for delivering precision medicine to patients. The remarkable efficacies of new targeted therapies have recently changed the paradigm for oncology to one of matching the right patient with the right therapy (1). This approach requires robust laboratory testing of patient samples. FDA-cleared tests exist for a limited number of markers (Table 1). In contrast, LDTs developed in CLIA-certified laboratories are used for >2000 genetic tests (2). LDTs are currently used in oncology for patient care and in clinical trials, which are now evaluating >500 agents targeting >100 genomic alterations. View this table: Table 1. Select list of CDx used for selection of targeted therapies.a The recent success in the development of 2 targeted therapies, crizotinib and vemurafenib, exemplifies the CDx process in which the FDA has co-cleared a diagnostic test (3, 4). The development of the CDx included analytical validation and elements of quality systems (good manufacturing practice, design control, personnel, software, instrumentation, and other parameters) as critical components of the regulatory package. The tests were used to recruit patients to pivotal phase II trials for the presence of the mutation/gene fusion. The …