The U.S. Food and Drug Administration has approved a new indication for gadobutrol (Gadavist) injection for intravenous use with magnetic resonance imaging (MRI) of the breast to assess the presence and extent of malignant breast disease. The approval is based on priority review of two multicenter phase III studies (GEMMA-1 and GEMMA-2) conducted in 13 countries.
Gadobutrol is a gadolinium-based extracellular contrast agent for MRI. It was first approved in the United States in March 2011 for intravenous use in diagnostic MRI in adults and children to detect and visualize areas with disrupted blood-brain barrier and/or abnormal vascularity of the central nervous system.
“The phase III GEMMA studies demonstrate that [gadobutrol]-enhanced breast MRI provided a statistically significant improvement in the identification of the extent of breast cancer vs unenhanced MRI,” said principal investigator Gillian Newstead, MD, FACR, from the University of Chicago Medical Center. “This is an important diagnostic tool for health-care professionals with breast cancer patients. Breast MRI with [gadobutrol] provides important visibility for assessment of malignant breast disease and for treatment planning.”
Two multicenter phase III clinical trials with identical design (GEMMA-1 and GEMMA-2) were used to investigate the diagnostic efficacy of gadobutrol-enhanced breast MRI. In total, 787 patients with recently diagnosed breast cancer from 13 countries were enrolled. In each study, MRI images were analyzed by three independent radiologists. These readers confirmed that gadobutrol-enhanced breast MRI improved ability to assess the presence and extent of breast cancer when compared to images from unenhanced breast MRI.
Gadobutrol-enhanced breast MRI demonstrated superior sensitivity (range, 80%–89%) for the presence and extent of malignant disease compared to unenhanced breast MRI (range, 37%–73%) for all six readers. A true-negative rate (specificity) of > 80% for breasts without malignant disease was confirmed for gadobutrol-enhanced breast MRI by five of six readers.
The studies did reveal that in breasts with malignancy, gadobutrol-enhanced breast MRI overestimated the histologically confirmed extent of malignancy in the diseased breast in up to 50% of patients. Three additional radiologists in each study read x-ray mammography alone. For these readers, over both studies, sensitivity for the presence and extent of malignancy ranged from 68% to 73% and specificity ranged from 86% to 94% in nonmalignant breasts.
Final study findings will be presented at an upcoming medical meeting. ■