The evidence framework for precision cancer medicine.

Precision cancer medicine (PCM) is a concept in which oncologists increasingly strive to tailor the use of targeted therapies in order to match the complexity of the cancer genome. This approach contradicts the historical framework used to support oncology practice that requires evidence from randomized controlled trials in order to change standards of care. This contrast demonstrates the irony of PCM: the therapies themselves are more precise than standard cytotoxic agents, although the clinical evidence supporting the benefits of these therapies is often considerably less precise. Nevertheless, the implementation of PCM should still be based on a framework of evidence-based development that supports clinical decision-making; this approach should not be simple off-label prescription of drugs following sequencing of a tumour biopsy sample. The clinical validation of increasingly complex diagnostic tests, the development of novel methods of evaluating efficacy, and the re-assessment of the standards of evidence sufficient to demonstrate the benefit of precision cancer therapies are all needed before PCM becomes the standard of care for patients with tumours harbouring genomic abnormalities of uncertain clinical significance.