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

MINDACT investigators and the TRANSBIG Consortium

doi:10.1200/JCO.19.01371

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

MINDACT investigators and the TRANSBIG Consortium

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	1186-1197
Number of pages	12
Journal	Journal of Clinical Oncology
Volume	38
Issue number	11
DOIs	https://doi.org/10.1200/JCO.19.01371
State	Published - 10 Apr 2020

Bibliographical note

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

Access to Document

10.1200/JCO.19.01371

Cite this

@article{6e41ed3f5f364c689feacabb36295858,

title = "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",

abstract = "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.",

author = "{MINDACT investigators and the TRANSBIG Consortium} and Suzette Delaloge and Martine Piccart and Emiel Rutgers and Saskia Liti{\`e}re and {van{\textquoteright}t Veer}, {Laura J.} and {van den Berkmortel}, Franchette and Etienne Brain and Aleksandra Dudek-Peric and Miguel Gil-Gil and Patricia Gomez and Hilbers, {Florentine S.} and Zaman Khalil and Susan Knox and Sherko Kuemmel and Georg Kunz and Anne Lesur and Pierga, {Jean Yves} and Peter Ravdin and Rubio, {Isabel T.} and Mahasti Saghatchian and Smilde, {Tineke J.} and Thompson, {Alastair M.} and Giuseppe Viale and Gabriele Zoppoli and Peter Vuylsteke and Konstantinos Tryfonidis and Coralie Poncet and Jan Bogaerts and Fatima Cardoso and Karen Benn and Eva Ciruelos and Sabine Corochan and Julia Cuny and {de la Pena}, Lorena and Mauro DeLorenzi and Inge Eekhout and Oleg Gluz and Vassilis Golfinopoulos and Theodora Goulioti and Nadia Harbeck and Val{\'e}rie Hilal and Jerome Lemonnier and Micha{\l} {\L}awniczak and Luca Marini and Erika Matos and Peppi Morales and Kirsten Murray and Urlike Nitz and Rodolfo Passalaqua and Carlos Castaneda",

note = "Publisher Copyright: {\textcopyright} 2020 by American Society of Clinical Oncology",

year = "2020",

month = apr,

day = "10",

doi = "10.1200/JCO.19.01371",

language = "Ingl{\'e}s",

volume = "38",

pages = "1186--1197",

journal = "Journal of Clinical Oncology",

issn = "0732-183X",

publisher = "American Society of Clinical Oncology",

number = "11",

}

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 - MINDACT investigators and the TRANSBIG Consortium

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 - Castaneda, Carlos

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.

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 - Artículo

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 -

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

Abstract

Bibliographical note

Access to Document

Other files and links

Fingerprint

Cite this