Background: Biomarkers have become enormously important in oncology in recent years. As so-called "personalised medicine" they support clinical decisions to assess patients, i.e. their tumours, with regard to response to therapies. Multi-gene panels (such as FoundationOne®Cdx) are just starting to be offered for comprehensive molecular-genetic tumour profiling, enabling the simultaneous analysis of a few to several hundred genetic alterations in disease genes. The health policy issue is whether multi-gene diagnostics using gene panels will lead to better clinical outcomes than conventional, single-biomarker stratification.

Methods: To answer the research questions, a systematic literature search for FoundationOne®Cdx was carried out, the manufacturer contacted, and a hand search for further information conducted.

Results: The European Medicines Agency (EMA) has approved 31 are oncology drugs for which a biomarker-based companion diagnostic test is required or recommended. In the last 20 years, eight biomarkers have been identified and validated in clinical trials, some of them post hoc, some of them prospective. Especially for tumours with a high mutation rate (such as NSCLC), further biomarkers are currently being intensively researched. The majority of solid tumours (54-96%) show multiple genetic alterations, suggesting that 2-2.6 potential treatment options (approved AND currently under research) may be proposed for each patient. These potential treatment options are mostly (62-92%) used off-label. Only a small percentage of the 324 genes analysed in FoundationOne®CDx are currently relevant for approved drugs. No comparative clinical studies on the added benefit of FoundationOne®CDx compared to current clinical practice could be identified. Therefore, no conclusions can be made on the patient-relevant benefit of FoundationOne®CDx.

Conclusion: Currently, there is no scientific evidence that diagnostics with multi-gene panels for the development of therapy recommendations lead to better clinical outcomes. Few biomarkers are validated and recommended by the EMA, as well as by the FDA. Many more are at a research stage, although many expectations and hopes are being raised for multi-gene panels. It can be predicted that multi-gene panels will have the potential to stimulate a broad off-label use of drugs without having to test them for clinical relevance in clinical trials. These consequences should be given attention, as many approved oncology medications only have a marginal benefit (0-2 according to ESMO Magnitude of Clinical Benefit Scale) and may represent a potential therapeutic option, but have little actual clinical relevance.