Adjuvant docetaxel, doxorubicin, and cyclophosphamide in node-positive breast cancer: 10-year follow-up of the phase 3 randomised BCIRG 001 trial

John R. Mackey, Miguel Martin, Tadeusz Pienkowski, Janusz Rolski, Jean Paul Guastalla, Amer Sami, John Glaspy, Eva Juhos, Andrew Wardley, Tommy Fornander, John Hainsworth, Robert Coleman, Manuel R. Modiano, Jeferson Vinholes, T. Pintér, Álvaro Rodríguez-Lescure, Bruce Colwell, Pierre Whitlock, Louise Provencher, Kara LaingDavid Walde, Chris Price, Judith C. Hugh, Barrett H. Childs, Kimberly Bassi, Mary Ann Lindsay, Véronique Wilson, Matthieu Rupin, Vincent Houé, Charles Vogel

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126 Citations (Scopus)

Abstract

Background: We compared standard adjuvant anthracycline chemotherapy with anthracycline-taxane combination chemotherapy in women with operable node-positive breast cancer. Here we report the final, 10-year follow-up analysis of disease-free survival, overall survival, and long-term safety. Methods: BCIRG 001 was an open label, phase 3, multicentre trial in which 1491 patients aged 18-70 years with node-positive, early breast cancer and a Karnofsky score of 80% or more were randomly assigned to adjuvant treatment with docetaxel, doxorubicin, and cyclophosphamide (TAC) or fluorouracil, doxorubicin, and cyclophosphamide (FAC) every 3 weeks for six cycles. Randomisation was stratified according to institution and number of involved axillary lymph nodes per patient (one to three vs four or more). Disease-free survival was the primary endpoint and was defined as the interval between randomisation and breast cancer relapse, second primary cancer, or death, whichever occurred first. Efficacy analyses were based on the intention-to-treat principle. BCIRG 001 is registered with ClinicalTrials.gov, number NCT00688740. Findings: Enrolement took place between June 11, 1997 and June 3, 1999; 745 patients were assigned to receive TAC and 746 patients were assigned to receive FAC. After a median follow-up of 124 months (IQR 90-126), disease-free survival was 62% (95% CI 58-65) for patients in the TAC group and 55% (51-59) for patients in the FAC group (hazard ratio [HR] 0·80, 95% CI 0·68-0·93; log-rank p=0·0043). 10-year overall survival was 76% (95% CI 72-79) for patients in the TAC group and 69% (65-72) for patients in the FAC group (HR 0·74, 0·61-0·90; log-rank p=0·0020). TAC improved disease-free survival relative to FAC irrespective of nodal, hormone receptor, and HER2 status, although not all differences were significant in these subgroup analyses. Grade 3-4 heart failure occurred in 26 (3%) patients in the TAC group and 17 (2%) patients in the FAC group, and caused death in two patients in the TAC group and four patients in the FAC group. A substantial decrease in left ventricular ejection fraction (defined as a relative decrease from baseline of 20% or more) was seen in 58 (17%) patients who received TAC and 41 (15%) patients who received FAC. Six patients who received TAC developed leukaemia or myelodysplasia, as did three patients who received FAC. Interpretation: Our results provide evidence that the initial therapeutic outcomes seen at the 5-year follow-up with a docetaxel-containing adjuvant regimen are maintained at 10 years. However, a substantial percentage of patients had a decrease in left ventricular ejection fraction, probably caused by anthracycline therapy, which warrants further investigation. Funding: Sanofi.

Original languageEnglish
Pages (from-to)72-80
Number of pages9
JournalThe Lancet Oncology
Volume14
Issue number1
DOIs
Publication statusPublished - Jan 2013

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docetaxel
Doxorubicin
Cyclophosphamide
Breast Neoplasms
Fluorouracil
Disease-Free Survival
Anthracyclines
Random Allocation
Stroke Volume

ASJC Scopus subject areas

  • Oncology

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Adjuvant docetaxel, doxorubicin, and cyclophosphamide in node-positive breast cancer : 10-year follow-up of the phase 3 randomised BCIRG 001 trial. / Mackey, John R.; Martin, Miguel; Pienkowski, Tadeusz; Rolski, Janusz; Guastalla, Jean Paul; Sami, Amer; Glaspy, John; Juhos, Eva; Wardley, Andrew; Fornander, Tommy; Hainsworth, John; Coleman, Robert; Modiano, Manuel R.; Vinholes, Jeferson; Pintér, T.; Rodríguez-Lescure, Álvaro; Colwell, Bruce; Whitlock, Pierre; Provencher, Louise; Laing, Kara; Walde, David; Price, Chris; Hugh, Judith C.; Childs, Barrett H.; Bassi, Kimberly; Lindsay, Mary Ann; Wilson, Véronique; Rupin, Matthieu; Houé, Vincent; Vogel, Charles.

In: The Lancet Oncology, Vol. 14, No. 1, 01.2013, p. 72-80.

Research output: Contribution to journalArticle

Mackey, JR, Martin, M, Pienkowski, T, Rolski, J, Guastalla, JP, Sami, A, Glaspy, J, Juhos, E, Wardley, A, Fornander, T, Hainsworth, J, Coleman, R, Modiano, MR, Vinholes, J, Pintér, T, Rodríguez-Lescure, Á, Colwell, B, Whitlock, P, Provencher, L, Laing, K, Walde, D, Price, C, Hugh, JC, Childs, BH, Bassi, K, Lindsay, MA, Wilson, V, Rupin, M, Houé, V & Vogel, C 2013, 'Adjuvant docetaxel, doxorubicin, and cyclophosphamide in node-positive breast cancer: 10-year follow-up of the phase 3 randomised BCIRG 001 trial', The Lancet Oncology, vol. 14, no. 1, pp. 72-80. https://doi.org/10.1016/S1470-2045(12)70525-9
Mackey, John R. ; Martin, Miguel ; Pienkowski, Tadeusz ; Rolski, Janusz ; Guastalla, Jean Paul ; Sami, Amer ; Glaspy, John ; Juhos, Eva ; Wardley, Andrew ; Fornander, Tommy ; Hainsworth, John ; Coleman, Robert ; Modiano, Manuel R. ; Vinholes, Jeferson ; Pintér, T. ; Rodríguez-Lescure, Álvaro ; Colwell, Bruce ; Whitlock, Pierre ; Provencher, Louise ; Laing, Kara ; Walde, David ; Price, Chris ; Hugh, Judith C. ; Childs, Barrett H. ; Bassi, Kimberly ; Lindsay, Mary Ann ; Wilson, Véronique ; Rupin, Matthieu ; Houé, Vincent ; Vogel, Charles. / Adjuvant docetaxel, doxorubicin, and cyclophosphamide in node-positive breast cancer : 10-year follow-up of the phase 3 randomised BCIRG 001 trial. In: The Lancet Oncology. 2013 ; Vol. 14, No. 1. pp. 72-80.
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abstract = "Background: We compared standard adjuvant anthracycline chemotherapy with anthracycline-taxane combination chemotherapy in women with operable node-positive breast cancer. Here we report the final, 10-year follow-up analysis of disease-free survival, overall survival, and long-term safety. Methods: BCIRG 001 was an open label, phase 3, multicentre trial in which 1491 patients aged 18-70 years with node-positive, early breast cancer and a Karnofsky score of 80{\%} or more were randomly assigned to adjuvant treatment with docetaxel, doxorubicin, and cyclophosphamide (TAC) or fluorouracil, doxorubicin, and cyclophosphamide (FAC) every 3 weeks for six cycles. Randomisation was stratified according to institution and number of involved axillary lymph nodes per patient (one to three vs four or more). Disease-free survival was the primary endpoint and was defined as the interval between randomisation and breast cancer relapse, second primary cancer, or death, whichever occurred first. Efficacy analyses were based on the intention-to-treat principle. BCIRG 001 is registered with ClinicalTrials.gov, number NCT00688740. Findings: Enrolement took place between June 11, 1997 and June 3, 1999; 745 patients were assigned to receive TAC and 746 patients were assigned to receive FAC. After a median follow-up of 124 months (IQR 90-126), disease-free survival was 62{\%} (95{\%} CI 58-65) for patients in the TAC group and 55{\%} (51-59) for patients in the FAC group (hazard ratio [HR] 0·80, 95{\%} CI 0·68-0·93; log-rank p=0·0043). 10-year overall survival was 76{\%} (95{\%} CI 72-79) for patients in the TAC group and 69{\%} (65-72) for patients in the FAC group (HR 0·74, 0·61-0·90; log-rank p=0·0020). TAC improved disease-free survival relative to FAC irrespective of nodal, hormone receptor, and HER2 status, although not all differences were significant in these subgroup analyses. Grade 3-4 heart failure occurred in 26 (3{\%}) patients in the TAC group and 17 (2{\%}) patients in the FAC group, and caused death in two patients in the TAC group and four patients in the FAC group. A substantial decrease in left ventricular ejection fraction (defined as a relative decrease from baseline of 20{\%} or more) was seen in 58 (17{\%}) patients who received TAC and 41 (15{\%}) patients who received FAC. Six patients who received TAC developed leukaemia or myelodysplasia, as did three patients who received FAC. Interpretation: Our results provide evidence that the initial therapeutic outcomes seen at the 5-year follow-up with a docetaxel-containing adjuvant regimen are maintained at 10 years. However, a substantial percentage of patients had a decrease in left ventricular ejection fraction, probably caused by anthracycline therapy, which warrants further investigation. Funding: Sanofi.",
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TY - JOUR

T1 - Adjuvant docetaxel, doxorubicin, and cyclophosphamide in node-positive breast cancer

T2 - 10-year follow-up of the phase 3 randomised BCIRG 001 trial

AU - Mackey, John R.

AU - Martin, Miguel

AU - Pienkowski, Tadeusz

AU - Rolski, Janusz

AU - Guastalla, Jean Paul

AU - Sami, Amer

AU - Glaspy, John

AU - Juhos, Eva

AU - Wardley, Andrew

AU - Fornander, Tommy

AU - Hainsworth, John

AU - Coleman, Robert

AU - Modiano, Manuel R.

AU - Vinholes, Jeferson

AU - Pintér, T.

AU - Rodríguez-Lescure, Álvaro

AU - Colwell, Bruce

AU - Whitlock, Pierre

AU - Provencher, Louise

AU - Laing, Kara

AU - Walde, David

AU - Price, Chris

AU - Hugh, Judith C.

AU - Childs, Barrett H.

AU - Bassi, Kimberly

AU - Lindsay, Mary Ann

AU - Wilson, Véronique

AU - Rupin, Matthieu

AU - Houé, Vincent

AU - Vogel, Charles

PY - 2013/1

Y1 - 2013/1

N2 - Background: We compared standard adjuvant anthracycline chemotherapy with anthracycline-taxane combination chemotherapy in women with operable node-positive breast cancer. Here we report the final, 10-year follow-up analysis of disease-free survival, overall survival, and long-term safety. Methods: BCIRG 001 was an open label, phase 3, multicentre trial in which 1491 patients aged 18-70 years with node-positive, early breast cancer and a Karnofsky score of 80% or more were randomly assigned to adjuvant treatment with docetaxel, doxorubicin, and cyclophosphamide (TAC) or fluorouracil, doxorubicin, and cyclophosphamide (FAC) every 3 weeks for six cycles. Randomisation was stratified according to institution and number of involved axillary lymph nodes per patient (one to three vs four or more). Disease-free survival was the primary endpoint and was defined as the interval between randomisation and breast cancer relapse, second primary cancer, or death, whichever occurred first. Efficacy analyses were based on the intention-to-treat principle. BCIRG 001 is registered with ClinicalTrials.gov, number NCT00688740. Findings: Enrolement took place between June 11, 1997 and June 3, 1999; 745 patients were assigned to receive TAC and 746 patients were assigned to receive FAC. After a median follow-up of 124 months (IQR 90-126), disease-free survival was 62% (95% CI 58-65) for patients in the TAC group and 55% (51-59) for patients in the FAC group (hazard ratio [HR] 0·80, 95% CI 0·68-0·93; log-rank p=0·0043). 10-year overall survival was 76% (95% CI 72-79) for patients in the TAC group and 69% (65-72) for patients in the FAC group (HR 0·74, 0·61-0·90; log-rank p=0·0020). TAC improved disease-free survival relative to FAC irrespective of nodal, hormone receptor, and HER2 status, although not all differences were significant in these subgroup analyses. Grade 3-4 heart failure occurred in 26 (3%) patients in the TAC group and 17 (2%) patients in the FAC group, and caused death in two patients in the TAC group and four patients in the FAC group. A substantial decrease in left ventricular ejection fraction (defined as a relative decrease from baseline of 20% or more) was seen in 58 (17%) patients who received TAC and 41 (15%) patients who received FAC. Six patients who received TAC developed leukaemia or myelodysplasia, as did three patients who received FAC. Interpretation: Our results provide evidence that the initial therapeutic outcomes seen at the 5-year follow-up with a docetaxel-containing adjuvant regimen are maintained at 10 years. However, a substantial percentage of patients had a decrease in left ventricular ejection fraction, probably caused by anthracycline therapy, which warrants further investigation. Funding: Sanofi.

AB - Background: We compared standard adjuvant anthracycline chemotherapy with anthracycline-taxane combination chemotherapy in women with operable node-positive breast cancer. Here we report the final, 10-year follow-up analysis of disease-free survival, overall survival, and long-term safety. Methods: BCIRG 001 was an open label, phase 3, multicentre trial in which 1491 patients aged 18-70 years with node-positive, early breast cancer and a Karnofsky score of 80% or more were randomly assigned to adjuvant treatment with docetaxel, doxorubicin, and cyclophosphamide (TAC) or fluorouracil, doxorubicin, and cyclophosphamide (FAC) every 3 weeks for six cycles. Randomisation was stratified according to institution and number of involved axillary lymph nodes per patient (one to three vs four or more). Disease-free survival was the primary endpoint and was defined as the interval between randomisation and breast cancer relapse, second primary cancer, or death, whichever occurred first. Efficacy analyses were based on the intention-to-treat principle. BCIRG 001 is registered with ClinicalTrials.gov, number NCT00688740. Findings: Enrolement took place between June 11, 1997 and June 3, 1999; 745 patients were assigned to receive TAC and 746 patients were assigned to receive FAC. After a median follow-up of 124 months (IQR 90-126), disease-free survival was 62% (95% CI 58-65) for patients in the TAC group and 55% (51-59) for patients in the FAC group (hazard ratio [HR] 0·80, 95% CI 0·68-0·93; log-rank p=0·0043). 10-year overall survival was 76% (95% CI 72-79) for patients in the TAC group and 69% (65-72) for patients in the FAC group (HR 0·74, 0·61-0·90; log-rank p=0·0020). TAC improved disease-free survival relative to FAC irrespective of nodal, hormone receptor, and HER2 status, although not all differences were significant in these subgroup analyses. Grade 3-4 heart failure occurred in 26 (3%) patients in the TAC group and 17 (2%) patients in the FAC group, and caused death in two patients in the TAC group and four patients in the FAC group. A substantial decrease in left ventricular ejection fraction (defined as a relative decrease from baseline of 20% or more) was seen in 58 (17%) patients who received TAC and 41 (15%) patients who received FAC. Six patients who received TAC developed leukaemia or myelodysplasia, as did three patients who received FAC. Interpretation: Our results provide evidence that the initial therapeutic outcomes seen at the 5-year follow-up with a docetaxel-containing adjuvant regimen are maintained at 10 years. However, a substantial percentage of patients had a decrease in left ventricular ejection fraction, probably caused by anthracycline therapy, which warrants further investigation. Funding: Sanofi.

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