Abstract P5-14-03: Adjuvant dose dense doxorubicin-cyclophosphamide (ddAC) or docetaxel-AC (TAC) for high-risk breast cancer: First results of the randomized MATADOR trial (BOOG-2004-04)
Authors: van Rossum AGH , Oosterkamp HM , van Werkhoven E , Opdam M , Mandjes IAM , van Leeuwen-Stok E , van Tinteren H , Kok M , Imholz ALT , Portielje JEA , Bos MMEM , van Bochove A , Wesseling J , Rutgers EJ , Rodenhuis S , Linn SC 
Published: May 2019

Abstract
Background: Anthracycline-based adjuvant chemotherapy has substantially improved breast cancer survival. Both the addition of taxanes as well as using a dose dense treatment schedule can further ameliorate outcome, but inter-individual differences exist. Here we present the efficacy and toxicity of dose dense scheduled doxorubicin/cyclophosphamide (ddAC) versus docetaxel/doxorubicin/cyclophosphamide (TAC), which is, to our knowledge, the first direct comparison of these treatment regimens.
Methods: In this Dutch, multicenter phase III trial (ISRCTN61893718), patients with pT1-3, pN0-3, M0 breast cancer were randomized between six cycles of either A60C600 every 2 weeks or T75A50C500 every 3 weeks. All patients received pegfilgrastim. Patients were evaluated for recurrence-free survival (RFS) and overall survival (OS). Survival was compared in a Cox regression analysis and adjusted for known prognostic factors. These factors include age, type of surgery, tumor size, histological grade, ER/PR status, HER2 status, and lymph node status. Adverse events were reported according to the common toxicity criteria (CTCAE version 3.0).
Results: Between 2004 and 2012, 664 patients were enrolled of whom 531 (80%) had node positive disease. At a median follow up of 5 years, OS was 92% in the ddAC treated subgroup and 93% in the TAC treated subgroup (adjusted hazard ratio [HR] 0.75, 95% confidence interval [CI] 0.42-1.34, intention to treat population). Forty-two breast-cancer specific deaths were equally divided over both treatment arms. Similarly, no significant difference in RFS was observed between both treatment groups (adjusted HR 0.85, 95% CI 0.55-1.32). Molecular subtypes were defined by St. Gallen criteria: 548 patients (83%) had estrogen receptor positive disease and 102 patients (15%) triple negative disease. No heterogeneity regarding treatment efficacy was observed in these subtypes. In particular, there was no survival benefit for ddAC or TAC in the triple negative subtype. Both treatment regimens were well tolerated. Whereas anemia was more frequent in ddAC treated patients (19% vs 4.7%; p&lt;0.001), peripheral neuropathy occurred more frequently in TAC treated patients (4.6% vs 14.4%; p&lt;0.001). The frequency of febrile neutropenia was not significantly different between the treatment arms (11% vs 12.5%; n.s.). Six patients developed congestive heart failure: 2 ddAC treated patients, 4 TAC treated patients. One ddAC treated patient and one TAC treated patient were diagnosed with acute myeloid leukemia after study treatment; another patient in the ddAC treatment group developed myelodysplastic syndrome.
Conclusions: At a median follow up of 5 years no significant survival differences were observed between adjuvant ddAC and TAC, in all patients and in molecular subgroups, including triple negative. Our findings are in line with the Oxford overview, which reported no significant differences between taxane-based chemotherapy and more, non-taxane based chemotherapy given in a dose dense schedule. ddAC could be a reasonable alternative for patients with a contra-indication for TAC.
Citation Format: van Rossum AGH, Oosterkamp HM, van Werkhoven E, Opdam M, Mandjes IAM, van Leeuwen-Stok E, van Tinteren H, Kok M, Imholz ALT, Portielje JEA, Bos MMEM, van Bochove A, Wesseling J, Rutgers EJ, Rodenhuis S, Linn SC. Adjuvant dose dense doxorubicin-cyclophosphamide (ddAC) or docetaxel-AC (TAC) for high-risk breast cancer: First results of the randomized MATADOR trial (BOOG-2004-04) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-14-03.