Abstract P1-13-01: Final results of the ASG1-3 study, a randomized phase III study comparing a standard dose chemotherapy with epirubicin/cyclophosphamide and paclitaxel with a dose dense regimen with epirubicin and paclitaxel

Abstract

Abstract Background Dose dense chemotherapy (DDT) has shown improvements of disease-free survival (DFS) and overall survival for primary breast cancer patients with a high risk of relapse. There are much less data about the effect of DDT in patients with intermediate risk of recurrence (1-3 positive axillary lymph nodes). Aim of this prospectively randomized trial was to investigate the superiority of a DDT schedule over a standard chemotherapy (ST) in primary breast cancer patients with 1-3 positive axillary lymph nodes. Methods The ASG1-3 study is a prospectively randomized, open label phase III study of the Adjuvant Study Group of the NOGGO association. Patients were eligible for the trial, if they had a primary invasive breast cancer (pT1-3) with 1-3 positive axillary lymph nodes and no evidence of distant metastases. Patients were randomized to an adjuvant therapy with either 4 cycles epirubicin (90mg/m2 body surface area, BSA) and cyclophosphamide (600mg/m2 BSA) q3w, followed by 4 cycles of paclitaxel (175mg/m2 BSA) referred to as ST or to a therapy with 4 cycles of epicubicin (120 mg/m2 BSA) q2w and primary G-CSF support followed by 4 cycles of paclitaxel (175mg/m2 BSA) q2w and primary G-CSF support referred to as DDT. Trastuzumab was not given in this study. The study was designed to show an increase of 70% DFS (ST) to 80% DFS (DDT) 5 years after randomization. Comparisons were conducted using Kaplan Meier estimates, log rank tests and Cox regression analyses. In an exploratory way, subgroup analyses were performed for HER2, hormone receptor status and grading using Cox regression models with interaction terms. Results A total of 936 patients were eligible for survival analysis, of which 465 were randomized to ST and 471 to DDT from 2001 to 2004. Patient characteristics were mainly well balanced, with patients being 52.5/52.1 years old, 71.9/78.1% being hormone receptor positive, 24.4/24.6% being HER2 positive and 38.6/38.8% having a tumor grade of 3 in the ST arm and DDT arm respectively. 53 events occurred after ST and 46 after DDT. Adjusted hazard ratio (HR) was 0.87 (95%CI: 0.57-1.35; p=0.54). 5 year DFS rates were 85% (ST) vs. 87% (DDT). Hematological toxicities were the most common grade 3 or 4 adverse events. Grade 3/4 neutropenia occurred in 57.2 vs. 28.0%, grade 3/4 anemia in 15.3% vs. 17.1% and grade 3 /4 pain symptoms were seen in 13.2 vs. 12.4% of the patients in the ST arm vs. DDT arm respectively. Other grade 3/4 toxicities were less frequent than 10%. Subgroup analysis showed a significant interaction (p<0.001) between HER2 status and randomization arm with regard to DFS. In HER2 negative patients the HR was 1.53 (95%CI: 0.91-2.59), whereas in HER2 positive patients the HR was 0.22 (95%CI: 0.09-0.55). Patients with HER2 positive disease and DDT had a similar prognosis like HER2 negative patients. Conclusion In the overall population a statistically significant improvement of DFS could not be shown for the DDT arm. In patients with HER2 positive breast cancer DDT chemotherapy improved the disease-free survival to a prognosis which was similar to patients with HER2 negative disease. Citation Format: Fasching PA, Eggemann H, Krocker J, Häberle L, Volz B, Kleine-Tebbe A, Blohmer J-U, Kittel K, Hufnagel M, Janni W, Emons G, Simon E, Köhler U, Thomssen C, Kohls A, Beckmann MW, Hielscher C, Krabisch P, Zeiser T, Brodkorb T, Baier F, Nabieva N, Kellner S, Untch M, Stadie S, Budner M, Breitbach G-P, Keller M, Stickeler E, Kühn T, Tolkmitt M, Belau AK, Schmidt M, Ulm K, Kümmel S. Final results of the ASG1-3 study, a randomized phase III study comparing a standard dose chemotherapy with epirubicin/cyclophosphamide and paclitaxel with a dose dense regimen with epirubicin and paclitaxel [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-13-01.