Abstract P5-18-06: Trastuzumab can be safely administered concurrently with anthracycline for adjuvant treatment of HER2-positive breast cancer
Authors: Shen Songjie , Sun Qiang , Xu Ying , Zhou Yidong , Guan Jinghong , Mao Feng , Lin Yan , Wang Xuejing 
Published: May 2015

Abstract
Background Anthracycline and trastuzumab are the preferential choices in the treatment of HER2-positive breast cancer. Due to the unacceptably high rates of cardiotoxicity observed in the metastatic breast cancer, concurrent administration of anthracycline and trastuzumab (A+H) is contraindicated. However, in the neoadjuvant setting, A+H has shown high rates of pathological complete response and very low cardiotoxicity. So far, all the large adjuvant trials have only evaluated the sequential strategy of administration anthracycline and trastuzumab (A-H), whereas the safety and efficacy of A+H has never been evaluated prospectively. Thus, we conducted a prospective study to evaluate the cardiac safety and efficacy of A+H regimen in the adjuvant treatment of HER2-positive breast cancer.
Methods This is a prospective, randomized and controlled trial. Participants, with HER2-positive, operable breast cancer, but without previous neoadjuvant treatment, were randomized to receive adjuvant A+H or A-H. If anthracycline was administered alone or sequentially to taxane, the dose of doxorubicin and epirubicin was 60mg/m2 and 90-100mg/m2, respectively. If anthracycline was given concurrently with taxane, the dose of doxorubicin and epirubicin was 50mg/m2 and 75mg/m2, respectively. Trastuzumab was given every 3 weeks (loading dose of 8mg/kg, followed by 6mg/kg) for one year. Left ventricular ejection fraction (LVEF) was monitored by echocardiogram (ECHO) at baseline (before chemotherapy) and 3, 6, 9, 12 and 24 months after the initial dose of trastuzumab. The primary endpoint was cardiac safety. The second endpoints were disease-free survival (DFS) and overall survival. ClinicalTrials.gov ID: NCT01413828.
Results Between August 2011 and March 2014, 196 HER2-postive breast cancer patients (98 in the A+H group and 98 in the A-H group) were enrolled and randomized. Women in the two groups had similar baseline characteristics including age, tumor stage, hormonal receptor status, chemotherapy regimen, radiation therapy and endocrine therapy. Trastuzumab was well-tolerated in both groups and the primary cardiac event was asymptomatic decrease in LVEF. In the A+H group, there were 11 (11.2%) patients showed more than 10% but less than 20% reduction in LVEF (NCI-CTC Grade I). In the A-H group, there were 14 (14.3%) patients showed NCI-CTC Grade I LVEF reduction and 1 (1.0%) patient showed more than 20% reduction in LVEF (NCI-CTC Grade II). There was no case of congestive heart failure. The difference of the rates of cardiac events between the two groups was not significant (P=0.400). The mean LVEF of the baseline and 3, 6, 9, 12 and 24 months after initial dose of trastuzumab also showed no difference between the two groups. Patients in both groups had excellent disease control at a median follow up of 16 months. There were numerically more DFS events in the A-H group (6/98, 6.1%) than the A+H group (10/98, 10.2%), but the difference of DFS did not reach the statistical significance (P=0.485). There was no death in both groups.
Conclusions Trastuzumab administered concurrently with anthracycline is a safe adjuvant regimen and might improve the survival of patients with HER2-positvie breast cancer.
Citation Format: Songjie Shen, Qiang Sun, Ying Xu, Yidong Zhou, Jinghong Guan, Feng Mao, Yan Lin, Xuejing Wang. Trastuzumab can be safely administered concurrently with anthracycline for adjuvant treatment of HER2-positive breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-18-06.