Phase III Randomized Trial Comparing Doxorubicin and Cyclophosphamide Followed by Docetaxel (AC→T) with Doxorubicin and Cyclophosphamide Followed by Docetaxel and Trastuzumab (AC→TH) with Docetaxel, Carboplatin and Trastuzumab (TCH) in Her2neu Positive Early Breast Cancer Patients: BCIRG 006 Study.

Abstract

Background: Evaluation of the long-term benefit of biologically-based regimens of trastuzumab in the early breast cancer population, and optimization of trastuzumab integration to maximize efficacy and minimize cardiac toxicity.Material and Methods: We randomized HER2-positive (FISH+) breast cancer patients with axillary lymph node positive or high risk negative, to either standard AC (60/600 mg/m2 q3wk x4) followed by T (100 mg/m2 q3wk x 4) or two trastuzumab-containing regimens; AC followed by T with trastuzumab x 1 year or TCarbo (75 mg/m2/AUC6 q3wk x 6) with trastuzumab x 1 year. Patients were prospectively stratified by number of positive nodes (0, 1-3 vs 4+) and hormone receptor status. Patients with ER and/or PR positive (HR+) tumors received hormone-directed therapy for 5 yrs after chemotherapy. The primary endpoint was disease-free survival (DFS) with 80% power (0.05 significance level) to detect an absolute difference of 7%. Secondary endpoints include overall survival (OS) and safety, including cardiac toxicity (symptomatic events and asymptomatic LVEF decline). The first two protocol-specified analyses for this study were performed at 300 and 450 disease-related events. We now report the results of the third protocol-specified analysis conducted after 650 events, expected by end of June 2009.Results: A total of 3222 patients (1072 in AC-T, 1076 in AC-TH and 1074 in TCH) were recruited between April 2001 and March 2004. Baseline characteristics of the study population will be included. Cox analysis of DFS and OS (unadjusted and adjusted for nodal status) and cardiac toxicity data will be presented for the three treatment arms.Discussion: The results of this trial help define the role of trastuzumab in the breast cancer HER2-positive adjuvant setting, as well as the risks/benefits of adjuvant trastuzumab within the context of overall safety including cardiac toxicity. This latter objective is of particular importance given that many of these women may be cured of their disease in the adjuvant setting. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 62.

Lapatinib, a HER2 tyrosine kinase inhibitor, induces stabilization and accumulation of HER2 and potentiates trastuzumab-dependent cell cytotoxicity

“…Trastuzumab, a humanized monoclonal antibody directed at the extracellular domain of HER2, is active in patients with HER2-overexpressing metastatic breast cancer, reducing relapse-free survival and improving overall survival (Baselga et al, 1996;Slamon et al, 2001;Marty et al, 2005). Recently, trastuzumab has also been found to be efficacious in the adjuvant setting (Piccart-Gebhart et al, 2005;Romond et al, 2005;Slamon et al, 2005). The mechanisms of action of trastuzumab are complex and not fully understood.…”

Perspectives and Attitudes on the Use of Adjuvant Chemotherapy and Trastuzumab in Older Adults with HER-2+ Breast Cancer: A Survey of Oncologists

“…Trastuzumab, a monoclonal antibody with affinity for the HER-2 extracellular domain, has demonstrated efficacy in the setting of both early-stage and metastatic breast cancer. Data from several large, randomized studies confirm longer disease-free survival and overall survival times with the combination of adjuvant trastuzumab and chemotherapy, compared with chemotherapy alone [2][3][4]. There are no studies to date reporting on the efficacy of single-agent trastuzumab treatment in the adjuvant setting of HER-2 ϩ breast cancer.…”

Differential response of triple‐negative breast cancer to a docetaxel and carboplatin‐based neoadjuvant treatment

“…The 4-year disease-free survival rates were 83%, 82%, and 77% for the ACTH, TCH, and AC groups, respectively. 27 Taken together, docetaxel was effective in all subgroups of patients with breast cancer who had different hormone receptor status and HER2 status. Thus, docetaxel was selected in our study as part of the neoadjuvant regimen for the treatment of patients with large, nonmetastatic breast cancer.…”