Adjuvant Cyclophosphamide and Docetaxel With or Without Epirubicin for Early TOP2A-Normal Breast Cancer: DBCG 07-READ, an Open-Label, Phase III, Randomized Trial

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 -