Rapidly accruing knowledge of the mutational landscape of malignant neoplasms, the increasing facility of massively parallel genomic sequencing, and the availability of drugs targeting many "driver" molecular abnormalities have spurred the oncologic community to consider how to use these new tools to improve cancer treatment. In order to assure that assignment of patients to a particular targeted treatment is likely to be beneficial to the patient, it will be necessary to conduct appropriate clinical research. It is clear that clinical (histology and stage) eligibility criteria are not sufficient for most clinical trials using agents that target mutations that are present in only a minority of patients. Recently, several clinical trial designs have been suggested to test the benefit of targeted treatment in molecular and/or clinical subgroups of patients. However, challenges remain in the implementation of such trials, including choice of assay, levels of evidence regarding gene variants, tumor heterogeneity, identifying resistance mechanisms, the necessity of screening large numbers of patients, infrastructure needs, and collaboration of investigators and industry. This article reviews current trial designs and discusses some of the considerations, advantages, and drawbacks of designing clinical trials that depend on particular molecular variants as eligibility criteria.
©2015 American Association for Cancer Research.