Agendia Inc, Irvine, Calif, together with the European Organization for Research and Treatment of Cancer (EORTC) and Breast International Group (BIG), recently shared results of their “Microarray In Node-negative and 1 to 3 positive lymph node Disease may Avoid ChemoTherapy” (MINDACT) trial, demonstrating that the MammaPrint genomic assay can substantially reduce the use of adjuvant chemotherapy in patients with breast cancer.1
The MammaPrint test, used in risk assessment for women of all ages with early-stage breast cancer, identified a large group of patients for whom 5-year distant metastasis–free survival was equally good, regardless of whether they received adjuvant chemotherapy.
“The MINDACT trial design is the optimal way to prove clinical utility of a genomic assay,” says Laura van’t Veer, PhD, chief research officer at Agendia, and director of applied genomics at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center. “It gives the level 1A clinical evidence—prospective, randomized, and controlled—that empowers physicians to clearly and confidently know when chemotherapy is part of optimal early-stage breast cancer therapy. In this trial, MammaPrint was compared to the standard of care physicians use today, to decide what is the best treatment option for an early-stage breast cancer patient.”
The MINDACT trial is the first prospective, randomized, controlled clinical trial of a breast cancer recurrence genomic assay with level 1A clinical evidence, and the first prospective translational research study of this magnitude in breast cancer to report the results of its primary objective.
The trial included more than 3,300 patients who were categorized as having a high risk of breast cancer recurrence based on common clinical and pathological criteria. Among these patients, the MammaPrint assay reduced prescriptions for chemotherapy treatment by 46%. Using the 70-gene assay, 48% of lymph-node positive breast cancer patients considered clinically high-risk and genomic low-risk had a distant metastasis-free survival at 5 years in excess of 94%.
“Traditionally, physicians have relied on clinical-pathological factors such as age, tumor size, tumor grade, lymph node involvement, and hormone receptor status to make breast cancer treatment decisions,” says Massimo Cristofanilli, MD, associate director of translational research and precision medicine at the Robert H. Lurie Comprehensive Cancer Center at Northwestern University. “These findings provide level 1A clinical utility evidence by demonstrating that the detection of low-risk of distant recurrence reported by the MammaPrint test can be safely used in the management of thousands of women by identifying those who can be spared from a toxic and unnecessary treatment.”
MINDACT is a randomized phase III trial that investigates the clinical utility of MammaPrint, when compared to the standard clinical pathological criteria, for the selection of patients unlikely to benefit from adjuvant chemotherapy. From 2007 to 2011, 6,693 women who had undergone surgery for early-stage breast cancer enrolled in the trial. Participants were categorized as low- or high-risk for tumor recurrence in two ways: first, through analysis of tumor tissue using MammaPrint at a central location in Amsterdam; and second, using Adjuvant Online, a tool that calculates risk of breast cancer recurrence based on common clinical and biological criteria.
Patients characterized in both clinical and genomic assessments as “low-risk” were spared chemotherapy, while patients characterized as “high-risk” were advised chemotherapy. Those with conflicting results were randomized to use either clinical or genomic risk evaluation to decide on chemotherapy treatment.
The MINDACT trial is managed and sponsored by the EORTC as part of an extensive and complex partnership in collaboration with Agendia and BIG.
“Agendia will continue to collaborate with pharmaceutical companies, leading cancer centers, and academic groups on additional clinical research and in the pursuit of bringing more effective, individualized treatments within reach of cancer patients,” says Mark Straley, chief executive at Agendia. “We value the partnership with the EORTC and BIG, and it’s a great honor to share this critical milestone.”
- Piccart M, Rutgers E, van’ t Veer L, et al. Primary analysis of the EORTC 10041/BIG 3-04 MINDACT study: a prospective, randomized study evaluating the clinical utility of the 70-gene signature combined with common clinical-pathological criteria for selection of patients for adjuvant chemotherapy in breast cancer with 0 to 3 positive nodes [abstract]. Presented at the American Association for Cancer Research annual meeting (New Orleans: April 16–20, 2016). Available at: www.abstractsonline.com/Plan/ViewAbstract.aspx?mID=4017&sKey=33e51b6a-c17a-44b4-8d60-181308817ce7&cKey=59e341be-7abd-4de2-9c7f-d91835cc3d85&mKey=1d10d749-4b6a-4ab3-bcd4-f80fb1922267