Imaging Biomarkers and Surrogate Endpoints in Oncology Clinical Trials

Abstract

The imaging biomarkers concept has generated excitement for its potential impact on both drug development and clinical care. In early-stage drug development, preliminary efficacy data derived from imaging biomarkers may influence decisions on whether to promote candidate compounds to more expensive late-stage testing. In late-state testing, imaging biomarkers may help select patient subpopulations with higher drug efficacy and may provide surrogate endpoint data to support marketing applications to regulatory agencies. In the clinical setting, imaging biomarkers may help tailor targeted therapies to specific patient groups. Tumor size-based imaging biomarkers such as the Response Evaluation Criteria in Solid Tumors (RECIST) are the most widely used in human cancer imaging. Metabolic activity measurements from fluorodeoxyglucose positron emission tomography (FDG-PET) are now part of the current response assessment standards for hematologic malignancies and have also been incorporated minimally into the most recent revision of RECIST. The imaging community is now actively engaged in developing advanced imaging biomarkers to push response assessment to more fundamental metrics at the physiological, cellular, and molecular levels. Evaluation of new candidate biomarkers as possible surrogate endpoints for clinical trials requires addressing issues of analytical validation, qualification, and proper utilization.