Imaging Biomarker Applications in Oncology Drug Development
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Imaging Biomarker Applications in Oncology Drug Development
Janet C. Miller, DPhil Homer H. Pien, PhD A. Gregory Sorensen, MD Center for Biomarkers in Imaging, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts
Key Words Imaging; Biomarker; Cancer; Drug development; Clinical trial Correspondence Address A. Gregory Sorensen, MD, Center for Biomarkers in Imaging, Department of Radiology, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02129 (e-mail: [email protected] .harvard.edu).
At present, drug development is a long and costly process with an unacceptably high failure rate. As a result, both the Food and Drug Administration and the pharmaceutical industry have shown interest in using biomarkers of clinical response. Biomarker imaging is noninvasive, allows serial data collection, and lessens interpatient variability because each individual can serve as his or her own control. The only imaging biomarker currently accepted as a surrogate for clinical response is tumor shrinkage for accelerated approval. The imaging biomarker, 18F-fluoro-2-deoxy-D-glucose (FDG) and positron emission tomography (PET), is widely used clinically to assess response to therapy and, in some cases, corre-
INTRODUCTION Tumor shrinkage in response to therapy is widely recognized as having predictive value for the true clinical endpoint—prolonged survival. As a result, imaging changes in tumor size in response to therapy have long been used as an imaging biomarker in oncology drug development (1,2), giving advance information about the effectiveness of novel drugs. Since 1992, use of this biomarker has led to accelerated approval from the Food and Drug Administration (FDA) for most oncology products, although final approval requires follow-up survival data (3). Tumor shrinkage occurs over a period of months. Although this response can be determined sooner than prolonged survival, it can hardly be described as rapid and contributes to the lengthy time and high cost of bringing a drug to commercialization, which is estimated to be 12 years and nearly $1 billion (4). More rapid, accurate, and cost-effective means of predicting clinical outcome from therapy would translate not only into costs saved but would also weed out potential failures earlier.
lates better with prolonged survival than tumor shrinkage. Other biomarkers, such as hemodynamic biomarkers, have been used in early clinical trials as a means to assess bioactivity within hours or days of the start of treatment and to determine drug dose in subsequent trials. Many others have found applications in assessing bioactivity in preclinical stages of drug development. With further validation, many of these imaging biomarkers could become valuable in measuring response to therapy much faster than present methods. In addition, pharmacokinetic imaging will provide both clinical and preclinical data on uptake, distribution, and excretion of drug candidates.
Even though current drug development strategy is intended to eliminate unpromising d
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