Abstract OT2-22-01: Epirubicin, cyclophosphamide and pyrotinib followed by docetaxel, trastuzumab and pyrotinib as neoadjuvant therapy for stage II-III HER2-positive breast cancer: a single-arm, multicenter phase 2 trial
Authors: Shi Qiyun , Qi Xiaowei , Tang Peng , Fan Linjun , Chen Li , Wang Shushu , Zhang Guozhi , Wang Mengyuan , Che Hongying , Lv Pengwei , Chen Dejie , Hu Jinhui , Li Qiuyun , Zhang Yanwu , Yu Qiao , Yang Kunxian , Zhong Yuan , Chen Chuang , Zhou Zemin , Qian Liyuan , Zhang Jingwei , Ma Mingde , Sun Yi , Liu Jiangbo , Zhang Yi , Jiang Jun 
Published: March 2023

Abstract
Background: Dual HER2 targeted therapy with pyrotinib (a tyrosine kinase inhibitor targeting HER1, HER2, and HER4) and trastuzumab plus chemotherapy has been approved as neoadjuvant therapy for patients with HER2-positive breast cancer in China based on the results from phase 3 PHEDRA study. However, the optimal chemotherapy partner still needs exploration. This multicenter phase 2 trial (ChiCTR1900022293) aimed to investigate the efficacy and safety of epirubicin, cyclophosphamide and pyrotinib followed by docetaxel, trastuzumab and pyrotinib (ECP-THP) as neoadjuvant therapy for patients with stage II-III HER2-positive breast cancer. Methods: Patients received intravenous epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) on day 1 of each cycle for four 21-day cycles, followed by intravenous docetaxel (75 mg/m2) and trastuzumab (8 mg/kg loading dose, followed by 6 mg/kg) on day 1 for 4 cycles. Pyrotinib 400 mg was given orally once daily throughout the neoadjuvant therapy period. Surgery was performed within 16-20 days after the last neoadjuvant therapy. The primary endpoint was total pathological complete response (tpCR, ypT0/is ypN0) rate. Results: Between May 2020 and May 2022, a total of 175 patients enrolled. As of May 31, 2022, 144 patients had undergone surgery; the median age was 51 years (range, 26-67). Sixty-seven (46.5%) of 144 patients had hormone receptor (HR)-negative disease, and 77 (53.5%) had HR-positive disease. The tpCR rate was 67.4% (97/144; 95%CI, 59.3%-74.5%). Patients with HR-negative disease had numerically higher tpCR rate than those with HR-positive disease (73.1% [95%CI, 61.5%-82.3%] vs. 62.3% [95%CI, 51.2%-72.3%]), but without statistical significance (P=0.230). Miller-Payne grade 4 and 5 pathological responses were found in 22 (15.3%) and 97 (67.4%) of 144 patients, respectively. Regarding clinical response to neoadjuvant therapy before surgery, 31 (21.5%) of 144 patients achieved complete response and 99 (68.8%) achieved partial response, with an objective response rate of 90.3% (95%CI, 84.3%-94.1%). Of 161 patients with available safety data, the most common grade ≥3 adverse events included diarrhea (57.1%), white blood cell count decreased (8.7%), and neutrophil count decreased (5.6%). No treatment-related deaths occurred. Conclusions: Patients with stage II-III HER2-positive breast cancer show favorable clinical and pathological response to this ECP-THP neoadjuvant regimen, with an acceptable safety profile.
Citation Format: Qiyun Shi, Xiaowei Qi, Peng Tang, Linjun Fan, Li Chen, Shushu Wang, Guozhi Zhang, Mengyuan Wang, Hongying Che, Pengwei Lv, Dejie Chen, Jinhui Hu, Qiuyun Li, Yanwu Zhang, Qiao Yu, Kunxian Yang, Yuan Zhong, Chuang Chen, Zemin Zhou, Liyuan Qian, Jingwei Zhang, Mingde Ma, Yi Sun, Jiangbo Liu, Yi Zhang, Jun Jiang. Epirubicin, cyclophosphamide and pyrotinib followed by docetaxel, trastuzumab and pyrotinib as neoadjuvant therapy for stage II-III HER2-positive breast cancer: a single-arm, multicenter phase 2 trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-22-01.