New England Journal of Medicine Publishes MINDACT Trial Results Proving the Clinical Utility of MammaPrint® in Assisting Physicians to Identify Early-Stage Breast Cancer Patients who can Safely Forgo Chemotherapy
— 46% of patients identified as high risk for recurrence according to clinical-pathological factors as described in the publication, and who therefore would be usual candidates for adjuvant chemotherapy, were reclassified as Low Risk by MammaPrint® and MINDACT shows could possibly forgo chemotherapy[i] —
— MammaPrint could change clinical practice by providing critical prognostic information to aid in assessing patients’ risk for distant metastasis and potentially sparing over one hundred thousand women annually[ii] with early-stage breast cancer worldwide from unnecessary toxicities and side effects from chemotherapy and creating considerable cost savings —
— As demonstrated in the MINDACT trial, MammaPrint is now the only FDA-cleared breast cancer prognostic test with the highest level of evidence (1A) for its clinical utility to aid correctly identifying Low Risk patients —
IRVINE, CA and AMSTERDAM – 25 August 2016 – (HISPANICIZE WIRE) – Agendia, Inc., a world leader in personalized medicine and molecular cancer diagnostics, announces the peer-reviewed publication of the primary outcome results of the Microarray In Node-negative and 1 to 3 positive lymph node Disease may Avoid ChemoTherapy (MINDACT) clinical trial in the prestigious New England Journal of Medicine (NEJM). [i, iii, iv] The publication demonstrates that 46% of breast cancer patients considered for chemotherapy, whose tumors are classified MammaPrint Low Risk, have excellent survival without chemotherapy, and can thus be candidates to avoid this toxic therapy. [i, pg. 717]
MINDACT is a collaboration between Agendia, the European Organization for Research and Treatment of Cancer (EORTC) and the Breast International Group (BIG). A unique phase III prospective, randomized, controlled study of 6,693 patients across 112 European cancer centers, MINDACT provides the highest level of clinical evidence (Level 1A) and confirms the clinical utility of using Agendia’s MammaPrint 70- gene breast cancer recurrence assay to help predict clinical outcome in women with early-stage breast cancer.
“When we developed MammaPrint, we knew we wanted to achieve the same level of evidence required for a typical pharmaceutical drug. That is why we are one of only a few diagnostic tests with FDA clearance and why we rigorously evaluated MammaPrint in the context of clinical-pathological factors in the randomized MINDACT trial,” said Prof. Laura van ’t Veer, Chief Research Officer at Agendia, and Leader, Breast Oncology Program, and Director, Applied Genomics at UCSF Helen Diller Family Comprehensive Cancer Center. “Now indeed, we have the only genomic assay with Level 1A evidence to help physicians more accurately predict risk of distant metastasis in patients with early-stage breast cancer.”
MINDACT is the first prospective translational clinical study of this magnitude in early-stage breast cancer to report the results of its primary objective and publish them in a peer-reviewed journal. At 5 years, patients who did not receive adjuvant chemotherapy but were classified as being at high risk for breast cancer recurrence based on clinical-pathological factors and as being at Low Risk based on MammaPrint, had similar rates of disease free survival. [i, pg. 717]
“The design of the MINDACT trial proves the clinical utility of the MammaPrint assay,” said Dr. Gabriel Hortobagyi, MD, FACP, FASCO Professor and Chair Emeritus of the Department of Breast Medical Oncology at the MD Anderson Cancer Center (MDACC) and Chair of the Agendia Inc. Medical Advisory Board. “The reporting of these conclusive results of the trial will now give physicians increased confidence that in using MammaPrint, their treatment decisions will be based on the highest level of clinical evidence and will minimize the incidence of over- or under-treatment.”
“We understand that a risk–benefit assessment and decisions with respect to the use of adjuvant chemotherapy are highly variable and personalized among physicians and individual patients. However, these findings provide clinical utility by demonstrating that MammaPrint’s accuracy in helping to detect patients with a low risk of distant recurrence could be safely used in the management of over one hundred thousand[ii] women and potentially spare them from unnecessary chemotherapy,” said Dr. William Audeh, Chief Medical Officer at Agendia. “The toxicities and side effects of chemotherapy may outweigh the potentially small and non-statistically significant benefit (1.5% 95% CI, 0.50 to 1.21; p = 0.27) of chemotherapy in women at high risk based on clinical factors but at Low Risk per MammaPrint. Thus, physicians and breast cancer patients may on an individual basis decide to avoid it.”
In MINDACT, when the authors looked at the patients with the most common type of breast cancer, hormone receptor positive, human epidermal growth factor receptor 2 negative, and lymph node negative (HR+/HER2-/LN0) disease, 75% were identified as having a Low Risk of recurrence using MammaPrint. The Distant Metastasis Free Interval (DMFI) for these patients (which according to the researchers is the optimal endpoint to evaluate a genomic assay that looks at prognosis and benefit of chemotherapy treatment) was 97.8% without chemotherapy. [i, supplement pg. 12-13]
In MINDACT, this MammaPrint Low Risk group of breast cancer patients who may be candidates to forgo chemotherapy is over four times larger than the proportion identified with a low-Recurrence Score® (RS) in both TAILORx.[v] and Plan B.[vi]. The TAILORx trial, which is the trial that would validate the appropriate cut-offs for the Oncotype DX® 21-gene breast cancer recurrence assay, has only reported data on the low risk arm of the study that included 15% of the patients who are in the non-randomized arm of patients with RS 10 and under. The TAILORx trial, has not presented results of its primary objective of the outcome of patients with RS between 11-25.
“MINDACT provides us with the highest level of evidence to support what we at Agendia have always believed, that MammaPrint is a definitive, accurate and clinically relevant breast cancer recurrence assay. The quality of life and cost efficiency implications of helping physicians choose the appropriate management for women with breast cancer is the reason we do what we do every day,” commented Mark Straley, Chief Executive Officer, Agendia. “We understand that ultimately, the decision to receive or forgo chemotherapy lies with each patient and physician who is properly informed about the potential side effects and benefits of such treatment. Nonetheless, MammaPrint could potentially change the standard of care and we look forward to its recommendation for inclusion in all early-stage breast cancer management guidelines. This will ensure that even more patients, physicians and healthcare systems are aware of the benefits of MammaPrint-based management decisions.”
Breast cancer is the most frequently diagnosed cancer in women worldwide.[vii] In 2012, there were nearly 1.7 million new breast cancer cases among women worldwide, accounting for 25% of all new cancer cases in women.[viii] MINDACT initial results were selected for a prestigious breakthrough presentation at the AACR Annual Meeting 2016, 16-20 April.
For more information on the MINDACT trial publication, please visit the Agendia newsroom: http://www.agendia.com/agendia-news-and-press-releases/
[i] Cardoso F, van’t Veer LJ, Bogaerts J et al. 70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer. N Engl J Med 2016; 375: 717-29.
[ii] Based on applying MINDACT risk data to: American Cancer Society. Global Cancer Facts & Figures 3rd Edition. Atlanta: American Cancer Society; 2015. (online) and American Cancer Society. Breast Cancer Facts & Figures 2015-2016. Atlanta: American Cancer Society, Inc. 2015.
[iii] Hudis CA, Dickler, M. Increasing Precision in Adjuvant Therapy for Breast Cancer. N Engl J Med 2016; 375: 790-91.
[iv] For disclosures regarding involvement in trial, see page 728 of publication (Cardoso F. NEJM 2016) mentioned above.
[v] Sparano JA, Gray RJ, Makower DF, et al. Prospective validation of a 21-gene expression assay in breast cancer. N Engl J Med 2015; 373: 2005-14.
[vi] Gluz O, Nitz, U. A., Matthias, C, et al. West German Study Group Phase III Plan B Trial: First Prospective Outcome Data for the 21-Gene Recurrence Score Assay and Concordance of Prognostic Markers by Central and Local Pathology Assessment. J Clin Oncol 2016; 34(20):2341-9
[vii] World Health Organization. Breast cancer: prevention and control. Website. http://www.who.int/cancer/detection/breastcancer/en/index1.html Accessed March 2016.
[viii] American Cancer Society. Global Cancer Facts & Figures 3rd Edition. Atlanta: American Cancer Society; 2015. (online)
MINDACT is a prospective, randomized, phase III, controlled clinical trial that investigates the clinical utility of MammaPrint, when used in conjunction with 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, across 112 centers in nine countries. Patients were categorized as low or high risk for tumor recurrence in two ways: first, through analysis of tumor tissue using MammaPrint; and second, using Adjuvant! Online, a tool that calculates risk of breast cancer recurrence based on common clinical pathological factors. Patients characterized in both clinical and genomic assessments as low risk are spared chemotherapy, while patients characterized as high risk are advised chemotherapy. Those with discordant results were randomized to use either clinical or genomic risk (MammaPrint) evaluation for chemotherapy treatment.
MINDACT is a population based trial. A risk–benefit assessment and decisions with respect to the use of chemotherapy are highly variable among physicians and patients, and even national and international guidelines differ in their recommendations. Ultimately, the decision to receive or forgo chemotherapy (or any other treatment) lies with each patient who is properly informed about the potential side effects and the potential benefits of such treatment. For the same risk–benefit scenario, different patients may make different decisions. [i, pg. 727-28]
MammaPrint is a FDA-cleared in vitro diagnostic test, performed in a single laboratory, using the gene expression profile of breast cancer tissue samples to assess a patients’ risk for distant metastasis. The MammaPrint result is indicated for use by physicians as a prognostic marker only, along with other clinical-pathological factors. MammaPrint is not intended for diagnosis, or to predict or detect response to therapy, or to help select the optimal therapy for patients. Results should be taken in the context of other relevant clinical-pathological factors and standard practice of medicine.
Agendia is a privately held, leading molecular diagnostics company that develops and markets FFPE- based genomic diagnostic products, which help support physicians with their complex treatment decisions. Agendia’s breast cancer and colorectal cancer tests were developed using an unbiased gene selection by analyzing the complete human genome. Our offerings include the FDA-cleared MammaPrint FFPE 70-gene breast cancer recurrence assay as well as BluePrint®, a molecular subtyping assay that provides deeper insight leading to more clinically actionable breast cancer biology. These tests can help physicians assess a patient’s individual risk for metastasis – that is, which patients are more sensitive to chemo, hormonal, or combination therapy, and which patients may not require these treatments and which patients may be treated with other, less arduous and costly methods.
In addition, Agendia has a pipeline of other genomic products in development. The company collaborates with pharmaceutical companies, leading cancer centers and academic groups to develop companion diagnostic tests in the area of oncology. For more information, visit www.agendia.com.