TY - JOUR
T1 - Standard anthracycline based versus docetaxel-capecitabine in early high clinical and/or genomic risk breast cancer in the EORTC 10041/BIG 3-04 MINDACT phase III trial
AU - Delaloge, Suzette
AU - Piccart, Martine
AU - Rutgers, Emiel
AU - Litière, Saskia
AU - van’t Veer, Laura J.
AU - van den Berkmortel, Franchette
AU - Brain, Etienne
AU - Dudek-Peric, Aleksandra
AU - Gil-Gil, Miguel
AU - Gomez, Patricia
AU - Hilbers, Florentine S.
AU - Khalil, Zaman
AU - Knox, Susan
AU - Kuemmel, Sherko
AU - Kunz, Georg
AU - Lesur, Anne
AU - Pierga, Jean Yves
AU - Ravdin, Peter
AU - Rubio, Isabel T.
AU - Saghatchian, Mahasti
AU - Smilde, Tineke J.
AU - Thompson, Alastair M.
AU - Viale, Giuseppe
AU - Zoppoli, Gabriele
AU - Vuylsteke, Peter
AU - Tryfonidis, Konstantinos
AU - Poncet, Coralie
AU - Bogaerts, Jan
AU - Cardoso, Fatima
AU - Benn, Karen
AU - Ciruelos, Eva
AU - Corochan, Sabine
AU - Cuny, Julia
AU - de la Pena, Lorena
AU - DeLorenzi, Mauro
AU - Eekhout, Inge
AU - Gluz, Oleg
AU - Golfinopoulos, Vassilis
AU - Goulioti, Theodora
AU - Harbeck, Nadia
AU - Hilal, Valérie
AU - Lemonnier, Jerome
AU - Ławniczak, Michał
AU - Marini, Luca
AU - Matos, Erika
AU - Morales, Peppi
AU - Murray, Kirsten
AU - Nitz, Urlike
AU - Passalaqua, Rodolfo
AU - Mook, Stella
N1 - Funding 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.
Funding 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.
Funding Information:
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
Publisher Copyright:
© 2020 by American Society of Clinical Oncology
PY - 2020/4/10
Y1 - 2020/4/10
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Anthracyclines/administration & dosage
KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
KW - Breast Neoplasms/drug therapy
KW - Capecitabine/administration & dosage
KW - Docetaxel/administration & dosage
KW - Female
KW - Humans
KW - Middle Aged
KW - Prospective Studies
UR - http://www.scopus.com/inward/record.url?scp=85083003495&partnerID=8YFLogxK
U2 - 10.1200/JCO.19.01371
DO - 10.1200/JCO.19.01371
M3 - Article
C2 - 32083990
AN - SCOPUS:85083003495
SN - 0732-183X
VL - 38
SP - 1186
EP - 1197
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 11
ER -