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 language | English |
|---|---|
| Pages (from-to) | 72-80 |
| Number of pages | 9 |
| Journal | The Lancet Oncology |
| Volume | 14 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2013 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Oncology
Cite this
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; Pinter, Tamas; 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, 01.01.2013, p. 72-80.Research output: Contribution to journal › Article
}
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 - Pinter, Tamas
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 - 2013/1/1
Y1 - 2013/1/1
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.
UR - http://www.scopus.com/inward/record.url?scp=84871712569&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84871712569&partnerID=8YFLogxK
U2 - 10.1016/S1470-2045(12)70525-9
DO - 10.1016/S1470-2045(12)70525-9
M3 - Article
C2 - 23246022
AN - SCOPUS:84871712569
VL - 14
SP - 72
EP - 80
JO - The Lancet Oncology
JF - The Lancet Oncology
SN - 1470-2045
IS - 1
ER -