Abstract CT039: Primary analysis of the EORTC 10041/ BIG 3-04 MINDACT study: a prospective, randomized study evaluating the clinical utility of the 70-gene signature (MammaPrint) combined with common clinical-pathological criteria for selection of patients for adjuvant chemotherapy in breast cancer with 0 to 3 positive nodes
Authors: Piccart Martine , Rutgers Emiel , van’ t Veer Laura , Slaets Leen , Delaloge Suzette , Viale Giuseppe , Pierga Jean Yves , Vuylsteke Peter , Brain Etienne , Vrijaldenhoven Suzan , Neijenhuis P. , Coudert Bruno , Smilde Tineke , Gil Miguel , Thompson Alastair , Rubio Isabel , Passalaqua Rodolfo , Matos Erika , Nitz Urlike , Delorenzi Mauro , Thomas Geraldine , Goulioti Theodora , Straehle Carolyn , Tryfonidis Konstantinos , Bogaerts Jan , Cardoso Fatima ,   on behalf of TRANSBIG consortium and MINDACT investigators
Published: July 2016

Abstract
Background: The MINDACT TRIAL investigated the clinical utility of the 70-gene profile (MammaPrint®), when confronted to the standard clinical pathological (CP) criteria, for the selection of patients unlikely to benefit from adjuvant chemotherapy (CT).Methods: From 2007 to 2011, 11288 patients were screened in 112 centers from 9 countries, of whom 6693 were enrolled. Enrolled patients had undergone successful determination of their genomic risk G (with MammaPrint®) and clinical risk C (modified version Adjuvant! Online). Patients were evaluated as “low clinical risk”, if their 10-year disease specific survival (without CT or endocrine therapy (ET), as estimated by Adjuvant! Online, was greater than 88% for ER-positive patients, and greater than 92% for ER-negative patients. Patients characterized in both assessments as “low- risk” were spared CT while for those “high- risk”, CT was advised. Those with discordant results were randomized to use either C or G risk evaluation to decide on CT. The main hypothesis was that G-assay would outperform the C-criteria by reducing the administration of adjuvant CT without impairing outcome. The CT and ET regimen randomization will not be part of the current presentation. The primary endpoint for the CT (yes/no) decision was distant metastasis free survival (DMFS). Secondary endpoints were the proportion of women treated per C over G, the overall survival (OS) and disease free survival (DFS). In the G-low/C-high risk group, a null hypothesis of a 5-year DMFS of 92% was tested (one-sided a = 2.5%) in the patients who were randomized to use the 70-gene signature prognosis (no CT), and who complied with this “no CT” assignment. Results: Median age of enrolled patients was 55 years. Eighty percent were LN- negative. 58% had tumor size between 1 and 2cm, 88% were HR-positive and 10% were HER2 positive. The enrolled patients were categorized in 4 risk groups; G-low/C-low [2745 patients (41%)], G-high/C-low [592 (9%)], G-low/C-high [1550 (23%)] and G-high/C-high [1806 (27%)]. In the G-low/C-high group, 51% of patients were randomized to CT (49% to no CT) and in the G-high/C-low group 50% to CT. At 5- years, DMFS was 94.7% (95%CI, 92.5-96.2%) for patients who were C- high/ G- low and randomized to use G and received no CT. This CI exceeds 92%, thereby rejecting the primary null hypothesis of MINDACT. There was an absolute 14% reduction in adjuvant CT administration when using the G versus C treatment strategy. Conclusion: C-high/G-low patients had a 5-year DMFS rate in excess of 94%, whether they were randomized to adjuvant CT or no CT. Using the G assay for CT treatment decision led to a 14% reduction in adjuvant CT administration in MINDACT. When using the G assay MammaPrint® among the C-high patients, there was a 46% (1550/3356) reduction in CT prescription, providing level 1A evidence for the clinical utility of MammaPrint® for assessing the lack of a clinically relevant chemotherapy benefit in the clinically high risk (C-high) population.
Citation Format: Martine Piccart, Emiel Rutgers, Laura van’ t Veer, Leen Slaets, Suzette Delaloge, Giuseppe Viale, Jean Yves Pierga, Peter Vuylsteke, Etienne Brain, Suzan Vrijaldenhoven, P. Neijenhuis, Bruno Coudert, Tineke Smilde, Miguel Gil, Alastair Thompson, Isabel Rubio, Rodolfo Passalaqua, Erika Matos, Urlike Nitz, Mauro Delorenzi, Geraldine Thomas, Theodora Goulioti, Carolyn Straehle, Konstantinos Tryfonidis, Jan Bogaerts, Fatima Cardoso, on behalf of TRANSBIG consortium and MINDACT investigators. Primary analysis of the EORTC 10041/ BIG 3-04 MINDACT study: a prospective, randomized study evaluating the clinical utility of the 70-gene signature (MammaPrint) combined with common clinical-pathological criteria for selection of patients for adjuvant chemotherapy in breast cancer with 0 to 3 positive nodes. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT039.