TY - JOUR
T1 - Adjuvant Cyclophosphamide and Docetaxel With or Without Epirubicin for Early TOP2A-Normal Breast Cancer
T2 - DBCG 07-READ, an Open-Label, Phase III, Randomized Trial
AU - Ejlertsen, Bent
AU - Tuxen, Malgorzata K
AU - Jakobsen, Erik Hugger
AU - Jensen, Maj-Britt
AU - Knoop, Ann Soegaard
AU - Højris, Inger
AU - Ewertz, Marianne
AU - Balslev, Eva
AU - Danø, Hella
AU - Vestlev, Peter Michael
AU - Kenholm, Julia
AU - Nielsen, Dorte L
AU - Bechmann, Troels
AU - Andersson, Michael
AU - Cold, Søren
AU - Nielsen, Hanne Melgaard
AU - Maae, Else
AU - Carlsen, Dorte
AU - Mouridsen, Henning T
PY - 2017/8/10
Y1 - 2017/8/10
N2 - Purpose Administration of anthracycline and taxane therapy in the adjuvant setting is considered a standard for breast cancer. We evaluated a non-anthracycline-based regimen in TOP2A-normal patients. Patients and Methods In this multicenter, open-label, phase III trial, 2,012 women with early TOP2A-normal breast cancer and at least one high-risk factor were randomly assigned to receive six cycles of docetaxel (75 mg/m2) and cyclophosphamide (600 mg/m2) every 3 weeks (DC) or three cycles of epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) followed by three cycles of docetaxel (100 mg/m2; EC-D). The primary end point was disease-free survival (DFS) after a median of 5 years of follow-up. Secondary end points were patient-reported toxicity, overall survival (OS), and distant disease-free survival. Results At a median estimated potential follow-up of 69 months, 5-year DFS was 87.9% (95% CI, 85.6% to 89.8%) in the EC-D arm and 88.3% (95% CI, 86.1% to 90.1%) in the DC arm. There was no significant difference in the risk of DFS events (hazard ratio [HR], 1.00; 95% CI, 0.78 to 1.28; P = 1.00), distant disease-free survival (HR, 1.12; 95% CI, 0.86 to 1.47; P = .40), or mortality (HR, 1.15; 95% CI, 0.83 to 1.59; P = .41) in the intent-to-treat analysis. A significant interaction between menopausal status and treatment group was observed for DFS ( P = .04) but not for OS ( P = .07). Patients with grade 3 tumors derived most benefit from DC, and patients with grade 1 to 2 tumors derived most benefit from EC-D (DFS: interaction P = .02; and OS: interaction P = .03). Patients receiving EC-D reported significantly more stomatitis, myalgia or arthralgia, vomiting, nausea, fatigue, and peripheral neuropathy, whereas edema was more frequent after DC. Conclusion This study provides evidence to support no overall outcome benefit from adjuvant anthracyclines in patients with early TOP2A-normal breast cancer.
AB - Purpose Administration of anthracycline and taxane therapy in the adjuvant setting is considered a standard for breast cancer. We evaluated a non-anthracycline-based regimen in TOP2A-normal patients. Patients and Methods In this multicenter, open-label, phase III trial, 2,012 women with early TOP2A-normal breast cancer and at least one high-risk factor were randomly assigned to receive six cycles of docetaxel (75 mg/m2) and cyclophosphamide (600 mg/m2) every 3 weeks (DC) or three cycles of epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) followed by three cycles of docetaxel (100 mg/m2; EC-D). The primary end point was disease-free survival (DFS) after a median of 5 years of follow-up. Secondary end points were patient-reported toxicity, overall survival (OS), and distant disease-free survival. Results At a median estimated potential follow-up of 69 months, 5-year DFS was 87.9% (95% CI, 85.6% to 89.8%) in the EC-D arm and 88.3% (95% CI, 86.1% to 90.1%) in the DC arm. There was no significant difference in the risk of DFS events (hazard ratio [HR], 1.00; 95% CI, 0.78 to 1.28; P = 1.00), distant disease-free survival (HR, 1.12; 95% CI, 0.86 to 1.47; P = .40), or mortality (HR, 1.15; 95% CI, 0.83 to 1.59; P = .41) in the intent-to-treat analysis. A significant interaction between menopausal status and treatment group was observed for DFS ( P = .04) but not for OS ( P = .07). Patients with grade 3 tumors derived most benefit from DC, and patients with grade 1 to 2 tumors derived most benefit from EC-D (DFS: interaction P = .02; and OS: interaction P = .03). Patients receiving EC-D reported significantly more stomatitis, myalgia or arthralgia, vomiting, nausea, fatigue, and peripheral neuropathy, whereas edema was more frequent after DC. Conclusion This study provides evidence to support no overall outcome benefit from adjuvant anthracyclines in patients with early TOP2A-normal breast cancer.
KW - Adult
KW - Aged
KW - Antigens, Neoplasm/genetics
KW - Antineoplastic Combined Chemotherapy Protocols/adverse effects
KW - Breast Neoplasms/genetics
KW - Carcinoma, Ductal, Breast/genetics
KW - Chemotherapy, Adjuvant
KW - Cyclophosphamide/administration & dosage
KW - DNA Topoisomerases, Type II/genetics
KW - DNA-Binding Proteins/genetics
KW - Disease-Free Survival
KW - Epirubicin/administration & dosage
KW - Female
KW - Follow-Up Studies
KW - Humans
KW - Intention to Treat Analysis
KW - Mastectomy
KW - Menopause
KW - Middle Aged
KW - Neoplasm Grading
KW - Poly-ADP-Ribose Binding Proteins
KW - Survival Rate
KW - Taxoids/administration & dosage
U2 - 10.1200/JCO.2017.72.3494
DO - 10.1200/JCO.2017.72.3494
M3 - Journal article
C2 - 28661759
SN - 0732-183X
VL - 35
SP - 2639
EP - 2646
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 23
ER -
