Abstract P1-12-02: Sequential versus concurrent administration of epirubicin and docetaxel as adjuvant chemotherapy in women with high-risk axillary lymph node negative early breast cancer. An interim analysis of a multicenter randomized study from the Hellenic oncology research group
Authors: D Mavroudis, E Saloustros, I Boukovinas, P Papakotoulas, S Kakolyris, N Ziras, C Christophylakis, N Kentepozidis, E Timotheadou, G Rigas, I-I Varthalitis, K Kalbakis, S Agelaki, V Georgoulias
Journal: Cancer Research (2016)

Abstract Purpose: To compare the sequential versus the concurrent administration of epirubicin and docetaxel as adjuvant therapy in high risk axillary node negative women with early breast cancer. Patients and treatment: Women 18-75 years old with invasive breast adenocarcinoma surgically resected with no infiltrated axillary lymph nodes and absence of metastatic disease were randomized to receive 4 cycles of epirubicin 90mg/m2 followed by 4 cycles of docetaxel 75mg/m2 (sequential regimen) or 6 cycles of epirubicin 75mg/m2 followed by docetaxel 75mg/m2 (concurrent regimen). All chemotherapy cycles were administered every 21 days with prophylactic G-CSF support for days 3-10 only for the concurrent regimen. Stratification was based on menopausal status, tumor size and hormone receptor expression. By protocol amendment in 2008 women with HER2 positive tumors were excluded. The primary endpoint of the study was to compare the disease-free survival (DFS) at 5 years and 329 patients were scheduled to enroll on each arm. Results: Between 2001-2013, 658 women were randomized and received the sequential (n=329) or the concurrent (n=329) regimen. The median age was 53 and 52 years, premenopausal status 43.8% versus 44.1%, tumor size &amp;lt;2cm in 44.1% versus 44.4%, histological grade 3 tumor in 52% versus 53.5% and hormone receptor negative disease in 33.1% versus 37.4% of patients in the sequential and concurrent regimens, respectively. After a median follow up of 70.5 and 70 months, there were 29 (8.8%) versus 42 (12.8%) disease relapses (p=0.102) and 11 (3.3%) versus 19 (5.8%) deaths (p=0.135), in the sequential and concurrent arms, respectively. The median DFS has not yet been reached in either arm (p=0.053) and the 5-year DFS rates were 92.6% versus 88.2% for sequential and concurrent arms, respectively. Dose reduction was required in 1.2% versus 3% (p=0.001) of the treatment cycles in the sequential and concurrent arms, respectively. Toxicity included grade 2-4 neutropenia in 54% versus 41% (p=0.001), febrile neutropenia 2.7% versus 6.1% (p=0.06), anemia 12% versus 17% (p=0.07), nausea/vomiting 18.5% versus 12.4% (p=0.03) of patients in the sequential and concurrent arms, respectively. There were no toxic deaths. Conclusion: In this interim analysis both the efficacy and the toxicity profile seem to favor the sequential over the concurrent regimen. Citation Format: Mavroudis D, Saloustros E, Boukovinas I, Papakotoulas P, Kakolyris S, Ziras N, Christophylakis C, Kentepozidis N, Timotheadou E, Rigas G, Varthalitis I-I, Kalbakis K, Agelaki S, Georgoulias V. Sequential versus concurrent administration of epirubicin and docetaxel as adjuvant chemotherapy in women with high-risk axillary lymph node negative early breast cancer. An interim analysis of a multicenter randomized study from the Hellenic oncology research group. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-12-02.