PURPOSE MINDACT demonstrated that 46% of patients with early breast cancer at high clinical but low genomic risk on the basis of MammaPrint may safely avoid adjuvant chemotherapy. A second random assignment (R-C) compared docetaxel-capecitabine with an anthracycline-based regimen. PATIENTS AND METHODS R-C randomly assigned patients 1:1 between standard anthracycline-based regimens, with or without taxanes (control) and experimental docetaxel 75 mg/m2 intravenously plus oral capecitabine 825 mg/m2 two times per day for 14 days (DC) every 3 weeks for 6 cycles. The primary end point was disease-free survival (DFS). Secondary end points included overall survival and safety. RESULTS Of 2,832 patients, 1,301 (45%) were randomly assigned, and 97% complied with R-C assignment. In the control arm, 29.6% only received taxanes (0.5% of N0 patients). DFS events (n = 148) were much less than required (n = 422) as a result of a lower-than-expected accrual and event rate. At 5 years of median follow-up, DFS was not different between DC (n = 652) and control (n = 649; 90.7% [95% CI, 88% to 92.8%] v 88.8% [95% CI, 85.9% to 91.1%]; hazard ratio [HR], 0.83 [95% CI, 0.60 to 1.15]; P = .26). Overall survival (HR, 0.91 [95% CI, 0.54 to 1.53]) and DFS in the clinical high and genomic high-risk subgroup (86.1% v 88.1%; HR, 0.83 [95% CI, 0.58 to 1.21]) were similar in both arms. DC led to more grade 1 neuropathy (27.1% v 11.2%) and more grade 2 hand/foot syndrome (28.5% v 3.3%) and diarrhea (13.7% v 5.8%). Serious cardiac events occurred in 9 patients (control, n = 4; DC, n = 5). Fifty-three patients developed second cancers (control, n = 32; DC, n = 21; leukemia: 2 v 1). Five treatment-related deaths occurred (control, 2 [0.3%]; DC, 3 [0.5%]). CONCLUSION Although underpowered, this second randomization in MINDACT did not show any improvement in outcome or safety with the use of DC compared with anthracycline-based chemotherapy.
Bibliographical noteFunding Information:
MINDACT was supported by grants from the European Commission Framework Programme VI (FP6-LSHC-CT-2004-503426, TRANSBIG Network of Excellence), the Breast Cancer Research Foundation, Novartis, F Hoffman La Roche, Sanofi, Eli Lilly, Veridex, the US National Cancer Institute, the European Breast Cancer Council?Breast Cancer Working Group (for the MINDACT biobank), the Jacqueline Seroussi Memorial Foundation (2006 JSMF award), Prix Mois du Cancer du Sein (2004 award), Susan G Komen for the Cure (SG05-0922-02), Fondation Belge Contre le Cancer (SCIE 2005-27), Dutch Cancer Society, The Netherlands Genomics Initiative?Cancer Genomics Centre (2008-2012), Association Le Cancer du Sein, Parlons-en!, the Brussels Breast Cancer Walk-Run and the American Women?s Club of Brussels, NIF Trust, German Cancer Aid, the Grant Simpson Trust and Cancer Research UK, and La Ligue Nationale Contre Le Cancer. Also supported by the European Organization for Research and Treatment of Cancer Cancer Research Fund. Whole-genome analysis was provided in kind by Agendia.
The authors thank all patients and families who participated in this study. The authors are grateful to the European Commission Sixth Framework Programme (FP6-LSHC-CT-2004-503426), the European Community Seventh Framework Programme (HEALTH-F2-2009-223175 to the Collaborative Oncological Gene-environment Study), the Breast International Group AISBL, F Hoffmann-La Roche, Novartis, and Sanofi for supporting this independent European Organisation for the Research and Treatment of Cancer study. Special thanks to All national coordinating centers and Breast International Group groups participating in MINDACT (EORTC-BCG, GOIRC, NCRI-BCSG, SOLTI, UNICANCER-UCBG, WSG); Peter Ravdin, who kindly allowed the implementation of Adjuvant! Online In MINDACT to allow all patients included in the trial to have their clinical risk evaluated; Steering Committee members: Karen Benn, Jan Bogaerts, Fatima Cardoso, Eva Ciruelos, Sabine Corochan, Julia Cuny, Lorena de la Pena, Suzette Delaloge, Mauro DeLorenzi, Aleksandra Dudek-Peric, Inge Eekhout, Oleg Gluz, Vassilis Golfinopoulos, Theodora Goulioti, Nadia Harbeck, Valérie Hilal, Susan Knox, Jerome Lemonnier, Michał Ławniczak, Luca Marini, Erika Matos, Peppi Morales, Kirsten Murray, Urlike Nitz, Rodolfo Passalaqua, Martine Piccart, Jolanda Remmelzwaal, Isabel Rubio, Emiel Rutgers, Mahasti Saghatchian, Leen Slaets, Christos Sotiriou, Carolyn Straehle, Mark Straley, Nathalie Theron, Alastair Thompson, Konstantinos Tryfonidis, Renata Todeschini, Milanka Urunkar, Laura van ’t Veer, and Giuseppe Viale; Fellows: Kim Aalders, Jacques Bines, Philippe Bedard, Ivana
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