PMID- 37302393 OWN - NLM STAT- MEDLINE DCOM- 20230810 LR - 20230810 IS - 2296-5262 (Electronic) IS - 2296-5270 (Linking) VI - 46 IP - 7-8 DP - 2023 TI - Neoadjuvant Pyrotinib plus Trastuzumab, Docetaxel, and Carboplatin in Early or Locally Advanced Human Epidermal Receptor 2-Positive Breast Cancer in China: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial. PG - 303-311 LID - 10.1159/000531492 [doi] AB - INTRODUCTION: This multicenter, randomized, double-blind, placebo-controlled phase 2 trial compared the efficacy, and safety of adding pyrotinib to trastuzumab, docetaxel, and carboplatin versus placebo, trastuzumab, docetaxel, and carboplatin in Chinese patients with human epidermal receptor 2 (HER2)-positive early or locally advanced breast cancer (ClinicalTrials.gov identifier: NCT03756064). METHODS: Sixty-nine women with HER2-positive early (T1-3, N0-1, M0) or locally advanced breast cancer (T2-3, N2 or N3, M0; T4, any N, M0) were recruited from October 1, 2019, to June 1, 2021. Before surgery, patients received 6 cycles of orally pyrotinib (400 mg once per day), trastuzumab (8-mg/kg loading dose and 6-mg/kg maintenance doses), docetaxel (75 mg/m2), and carboplatin (AUC = 6 mg/mL.min) or orally placebo, trastuzumab, and docetaxel, and carboplatin every 3 weeks. The primary end point was independent review committee-assessed total pathologic complete response rate. The 2-sided Cochran-Mantel-Haenszel test, stratified by age, hormone receptor status, tumor stage, nodal status, cTNM stage, and Ki-67 level was used to compare rates between treatment groups. RESULTS: In total, 69 female patients were randomized (pyrotinib, 36; and placebo, 33; median age, 53 [31-69] years). In the intention-to-treat population, total pathologic complete response rates were 65.5% (19/29) in the pyrotinib group and 33.3% (10/30) in the placebo group (difference, 32.2%, p = 0.013). Diarrhea was been reported in 86.1% of patients (31/36) in the pyrotinib group as the most common adverse events (AEs) and 15.2% of patients (5/33) in the placebo group. But no grade 4 or 5 AEs were reported. CONCLUSION: Treatment with pyrotinib, trastuzumab, docetaxel, and carboplatin resulted in a statistically significant improvement in the total pathologic complete response rate versus placebo, trastuzumab, docetaxel, and carboplatin for the neoadjuvant treatment of HER2-positive early or locally advanced breast cancer in Chinese patients. Safety data were in line with the known pyrotinib safety profile and generally comparable between treatment groups. CI - (c) 2023 S. Karger AG, Basel. FAU - Ding, Yuqin AU - Ding Y AD - Department of Breast Surgery, Zhejiang Cancer Hospital, Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, Hangzhou, China. FAU - Mo, Wenju AU - Mo W AD - Department of Breast Surgery, Zhejiang Cancer Hospital, Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, Hangzhou, China. FAU - Xie, Xiaohong AU - Xie X AD - Department of Breast Surgery, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou, China. FAU - Wang, Ouchen AU - Wang O AD - Department of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. FAU - He, Xiangming AU - He X AD - Department of Breast Surgery, Zhejiang Cancer Hospital, Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, Hangzhou, China. FAU - Zhao, Shuai AU - Zhao S AD - Department of Breast Surgery, Zhejiang Cancer Hospital, Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, Hangzhou, China. FAU - Gu, Xidong AU - Gu X AD - Department of Breast Surgery, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou, China. FAU - Liang, Chenlu AU - Liang C AD - Department of Breast Surgery, Zhejiang Cancer Hospital, Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, Hangzhou, China. FAU - Qin, Chengdong AU - Qin C AD - Department of Breast Surgery, Zhejiang Cancer Hospital, Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, Hangzhou, China. FAU - Ding, Kaijing AU - Ding K AD - Department of Child psychology, Affiliated Mental Health Center and Hangzhou Seventh People's Hospital University School of Medicine, Hangzhou, China. FAU - Yang, Hongjian AU - Yang H AD - Department of Breast Surgery, Zhejiang Cancer Hospital, Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, Hangzhou, China. FAU - Ding, Xiaowen AU - Ding X AD - Department of Breast Surgery, Zhejiang Cancer Hospital, Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, Hangzhou, China. LA - eng SI - ClinicalTrials.gov/NCT03756064 PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20230609 PL - Switzerland TA - Oncol Res Treat JT - Oncology research and treatment JID - 101627692 RN - P188ANX8CK (Trastuzumab) RN - 15H5577CQD (Docetaxel) RN - BG3F62OND5 (Carboplatin) RN - 0 (pyrotinib) RN - EC 2.7.10.1 (Receptor, ErbB-2) RN - 0 (Antibodies, Monoclonal, Humanized) SB - IM MH - Humans MH - Female MH - Middle Aged MH - *Breast Neoplasms/pathology MH - Trastuzumab/adverse effects MH - Docetaxel/therapeutic use MH - Carboplatin/therapeutic use MH - Neoadjuvant Therapy MH - Receptor, ErbB-2 MH - Antibodies, Monoclonal, Humanized/therapeutic use MH - Antineoplastic Combined Chemotherapy Protocols/therapeutic use MH - Treatment Outcome OTO - NOTNLM OT - Breast cancer OT - Human epidermal receptor 2 OT - Neoadjuvant therapy OT - Phase II trial OT - Pyrotinib OT - Trastuzumab OT - Tyrosine kinase inhibitor EDAT- 2023/06/12 00:42 MHDA- 2023/08/10 06:42 CRDT- 2023/06/11 18:23 PHST- 2023/03/26 00:00 [received] PHST- 2023/05/16 00:00 [accepted] PHST- 2023/08/10 06:42 [medline] PHST- 2023/06/12 00:42 [pubmed] PHST- 2023/06/11 18:23 [entrez] AID - 000531492 [pii] AID - 10.1159/000531492 [doi] PST - ppublish SO - Oncol Res Treat. 2023;46(7-8):303-311. doi: 10.1159/000531492. Epub 2023 Jun 9.