Abstract The objective of this multicenter, single‐arm trial (ChiCTR1900022293) was to explore the efficacy and safety of neoadjuvant therapy with epirubicin, cyclophosphamide, and pyrotinib followed by docetaxel, trastuzumab, and pyrotinib (ECPy‐THPy) in the treatment of patients with stage II–III HER2‐positive breast cancer. The present study enrolled patients with stage II–III HER2‐positive breast cancer. Epirubicin and cyclophosphamide were administrated for four 21‐day cycles, followed by four cycles of docetaxel and trastuzumab. Pyrotinib was taken orally once per day throughout the treatment period. The primary endpoint was total pathological complete response (tpCR, ypT0/is ypN0) rate in the modified intention‐to‐treat (mITT) population. In total, 175 patients were included. The tpCR rate was 68.6% (95% CI, 60.7–75.8%), while the objective response rate was 89.1%. In the post‐hoc subgroup analysis, no association between clinical characteristics and the tpCR rate was observed. The most common grade ≥3 adverse events were diarrhea (54.3%), followed by white blood cell count decreased (5.1%), and neutrophil count decreased (4.6%). In conclusion, the neoadjuvant regimen with ECPy‐THPy showed promising pathological response and clinical benefits with an acceptable safety profile in patients with stage II–III HER2‐positive breast cancer.
Background: The combination of pyrotinib and trastuzumab plus docetaxel has demonstrated favorable clinical efficacy in previous studies, but the optimal chemotherapy partner has not been decided yet. The present study aimed to investigate the efficacy and safety of epirubicin, cyclophosphamide and pyrotinib followed by docetaxel, trastuzumab and pyrotinib (ECPy-THPy) as neoadjuvant therapy for patients with stage II-III HER2-positive breast cancer.Methods: In this multicenter, single-arm study, patients with stage II-III HER2-positive breast cancer were recruited for intravenous epirubicin and cyclophosphamide for four 21-day cycles, followed by four cycles of intravenous docetaxel and trastuzumab. Pyrotinib was given orally once daily throughout the neoadjuvant therapy period. The primary endpoint was total pathological complete response (tpCR, ypT0/is ypN0) rate. Other endpoints included objective response rate, survival outcomes and safety.Findings: Between May 2020 and May 2022, a total of 175 patients were enrolled, among which 156 patients underwent surgery with evaluable pathological data. Overall, the tpCR rate was 68.6% (107/156; 95%CI, 60.7%-75.8%) in the efficacy-evaluable set and the objective response rate was 89.1%. A post hoc subgroup analysis found no clinical characteristics that related to pCR. Of 175 patients with available safety data, the most common grade ≥3 AEs included diarrhea (54.3%), white blood cell count decreased (5.1%), and neutrophil count decreased (4.6%).Interpretation: Patients with stage II-III HER2-positive breast cancer showed favorable clinical and pathological response to this ECPy-THPy neoadjuvant regimen, with an acceptable safety profile.Trial Registration: Identifier: ChiCTR1900022293.Funding: Program of Military Medical Staff Innovation Plan of Army Medical University (XZ-2019-505-042) and Program of Young and Middle-aged Medical Top Talents of Chongqing (414Z393).Declaration of Interest: The authors declare no competing interests.Ethical Approval: The trial was carried out in accordance with the Declaration of Helsinki and the Guidelines for Good Clinical Practice. The ethics committee at each participating institution approved the study protocol. All participants gave written informed consent before study entry.
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.
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