The US Food and Drug Administration (US FDA) has granted approval for a new indication for Bayer HealthCare's Gadavist (gadobutrol) injection for intravenous use with MRI of the breast to assess the presence and extent of malignant breast disease. The approval is based on priority review of two, multi-centre, Phase 3 studies (GEMMA-1 and GEMMA-2) conducted in 13 countries.

“The phase 3 GEMMA studies demonstrate that Gadavist-enhanced breast MRI provided a statistically significant improvement in the identification of the extent of breast cancer versus unenhanced MRI,” said GEMMA Principal Investigator Gillian Newstead, M.D., F.A.C.R., from the University of Chicago Medical Centre. “This is an important diagnostic tool for healthcare professionals with breast cancer patients. Breast MRI with Gadavist provides important visibility for assessment of malignant breast disease and for treatment planning.”

“Recognizing an unmet medical need, the FDA’s priority review and swift action provides access to an advancement in breast cancer management in the United States,” said Christiane Pering, M.D., Head of Global Innovation for Bayer HealthCare Medical Care. “The GEMMA studies demonstrate Bayer’s commitment to improve breast cancer detection the leading cause of cancer-related deaths among women worldwide through radiologic advances such as Gadavist-enhanced breast MRI.”

Two, multi-centre, phase 3 clinical trials with identical design (GEMMA-1 and GEMMA-2) were used to investigate the diagnostic efficacy of Gadavist-enhanced breast MRI. In total, 787 patients with recently diagnosed breast cancer from 13 countries were enrolled (GEMMA-1: 390 women; GEMMA-2: 396 women and one man). In each study, MRI images were analysed by three independent radiologists. These readers confirmed that Gadavist-enhanced breast MRI improved ability to assess the presence and extent of breast cancer when compared to images from unenhanced breast MRI.

Key findings for these studies included: Gadavist-enhanced breast MRI demonstrated superior sensitivity (range: 80-89 percent) for the presence and extent of malignant disease compared to unenhanced breast MRI (range: 37-73 per cent) for all six readers; A true-negative rate (specificity) of >80 per cent for breasts without malignant disease was confirmed for Gadavist-enhanced breast MRI by 5 of 6 readers.

The studies did reveal that in breasts with malignancy, Gadavist-enhanced breast MRI overestimated the histologically confirmed extent of malignancy in the diseased breast in up to 50 per cent of the 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 per cent to 73 per cent and specificity ranged from 86 per cent to 94 per cent in non-malignant breasts.

According to the International Agency on Cancer Research, the specialised cancer agency of the World Health Organization, in 2012 1.7 million women were diagnosed with breast cancer. Since the agency’s 2008 estimates, the incidence of breast cancer has increased by more than 20 per cent and mortality has increased by 14 per cent. Breast cancer is the most common cause of cancer death among women around the world (522,000 deaths in 2012) and is the most frequently diagnosed cancer among women in 140 of 184 countries worldwide.

Gadavist (gadobutrol) injection was first approved in the US in March 2011 for intravenous use in diagnostic magnetic resonance imaging (MRI) in adults and children (2 years of age and older) to detect and visualise areas with disrupted blood brain barrier (BBB) and/or abnormal vascularity of the central nervous system.

Gadavist, also known as Gadovist and Gadovist 1.0 in other regions, is the United States (US) brand name of the aqueous solution of gadobutrol, a gadolinium (Gd)-based extracellular contrast agent for magnetic resonance imaging (MRI).

Gadovist was first approved in February 1998 for the indication “Contrast enhancement in cranial and spinal MRI” in Switzerland, followed by approvals in Australia, Canada, the European Union (EU), and other countries. Today, gadobutrol has been approved in more than 100 countries worldwide. Following the initial approvals of Gadovist for use in cranial and spinal MRI, it was approved for contrast enhancement in magnetic resonance angiography (MRA) in 2003 and CE-MRI of the liver and kidneys in 2007 in the EU and other countries. Since 2009 pediatric use of gadobutrol in children 2 years and older has been granted in more than 80 countries, including EU, US and Canada. In 2012, Gadovist was approved for use in CE-MRI of the whole body in adults and children in the EU followed by approvals in several further European, Asian and Latin American countries.