Abstract PS13-14: A randomized, opened, phase II trial assessing the efficacy and safety of ATH-TH(doxorubicin/docetaxel/trastuzumab followed by docetaxel/trastuzumab) versus TCH(docetaxel/carboplatin/trastuzumab) as neoadjuvant treatment in HER2-positive breast cancer
Authors: Wang Tao , Zhou Jin-Mei , Hao Xiao-Peng , Zhang Hui-Qaing , Zhang Shao-Hua , Bian Li , Jiang Ze-Fei 
Published: February 2021

Background: Because Pertuzumab hasn't been approved in China until 2020y, trastuzumab has been standard neoadjuvant treatment for HER2-positive breast cancer. But we don't know which is the optimal chemotherapy with or without anthracyclines in the trastuzumab-based HER2-blockade. We designed this clinical trial to compare efficacy and safety between anthracycline and carboplatin in combination with docetaxel and trastuzumab as neoadjuvant therapy. Methods: From Apr, 2013 to Apr, 2019, 124 patients were enrolled. 60 patients were randomly assigned to the ATH-TH group and 64 to the TCH group. The treatment plan is showed as following, 1. TCH group: Trastuzumab(8mg/kg loading dose followed by 6mg/kg maintenance dose on day 1 every 3 weeks) combined with carboplatin(AUC=6 on day1 every 3 weeks) and docetaxel (75mg/m2 d1 every 3 weeks), total 6 cycles ; 2. ATH-TH group: Trastuzumab combined with doxorubicin( 50mg/m2 on day1 every 3 weeks) and docetaxel (75mg/m2 d1 every 3 weeks) after 4 cycles, followed by Trastuzumab plus docetaxel (75mg/m2 d1 every 3 weeks) 4 cycles. Primary endpoint was pCR(ypT0/is/ypN0). Second endpoints included safety, event-free and overall survial (EFS and OS). This trial is registered with ClinicalTrials.gov, number NCT 02510781.Results: Baseline Patients’ characteristics were well balanced between ATH-TH group and TCH group: median age 49y/48y, hormone receptor positive 51.7% vs 46.9%, II stage 60.0% VS 64.0%, III stage 33.3% VS 32.8%. The pCR rate was no significant difference(P=0.457) in ATH-TH 56.7%(95% CI:43.8%-69.6% ) and TCH group 50.0% ( 95% CI :37.4%-62.6%) .In hormone positive subgroup, the pCR rate was 36.7% ( 95% CI:18.4%-55.0% )for TCH group, and 51.6% (95% CI:33.0%-70.2%) for ATH-TH group (P=0.24). In hormone negative subgroup, the pCR rate was 61.8% (95% CI:44.6%-79.0% )for TCH group, and 62.1% ( 95% CI:43.3%-80.9%) for ATH-TH group (P=0.98). The most common adverse events were hematologic toxicities. ATH-TH group had higher 3/4 grade leukocyte decrease rates than TCH group ( 86.7% VS 43.8%, p&lt;0.001) and higher 3/4 thrombocytopenia (11.7% VS 1.6%, p&lt;0.016). ATH-TH group had more FN than (43.3% VS 3.1%, p&lt;0.001). LVEF change and cardiac events were similar between two group Four-year EFS estimates were 94.5% for ATH-TH and 91.1% for TCH (p=0.768, HR=0.82, 95% CI: 0.22-3.06). Four-year OS estimates were 97.5% for ATH-TH and97.8%for TCH (p=0.562, HR=2.0, 95% CI: 0.18-22.2). Conclusions: This is the first prospective randomised trial compare neoadjuvant therapy regimen ATH-TH with TCH in HER2-positive breast cancer. We acquired similar pCR rate, four-year EFS and OS but less toxicity in TCH group compared with ATH-TH. Long-term follow-up is required to confirm these results. Clinical trial information: NCT 02510781. Research Sponsor: None

Citation Format: Tao Wang, Jin-Mei Zhou, Xiao-Peng Hao, Hui-Qaing Zhang, Shao-Hua Zhang, Li Bian, Ze-Fei Jiang. A randomized, opened, phase II trial assessing the efficacy and safety of ATH-TH(doxorubicin/docetaxel/trastuzumab followed by docetaxel/trastuzumab) versus TCH(docetaxel/carboplatin/trastuzumab) as neoadjuvant treatment in HER2-positive breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-14.