Letrozole; Ki-67 Antigen; pyrotinib; Receptor, ErbB-2; Protein Kinase Inhibitors; Humans; Female; Letrozole/therapeutic use; Receptor, ErbB-2/genetics; Receptor, ErbB-2/metabolism; Antineoplastic Combined Chemotherapy Protocols/adverse effects; Protein Kinase Inhibitors/therapeutic use; Neoadjuvant Therapy/methods; Breast Neoplasms/pathology; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Neoadjuvant Therapy; Chemistry (all); Biochemistry, Genetics and Molecular Biology (all); Multidisciplinary; Physics and Astronomy (all); General Physics and Astronomy; General Biochemistry, Genetics and Molecular Biology; General Chemistry
Abstract :
[en] Current therapies for HER2-positive breast cancer have limited efficacy in patients with triple-positive breast cancer (TPBC). We conduct a multi-center single-arm phase 2 trial to test the efficacy and safety of an oral neoadjuvant therapy with pyrotinib, letrozole and dalpiciclib (a CDK4/6 inhibitor) in patients with treatment-naïve, stage II-III TPBC with a Karnofsky score of ≥70 (NCT04486911). The primary endpoint is the proportion of patients with pathological complete response (pCR) in the breast and axilla. The secondary endpoints include residual cancer burden (RCB)-0 or RCB-I, objective response rate (ORR), breast pCR (bpCR), safety and changes in molecular targets (Ki67) from baseline to surgery. Following 5 cycles of 4-week treatment, the results meet the primary endpoint with a pCR rate of 30.4% (24 of 79; 95% confidence interval (CI), 21.3-41.3). RCB-0/I is 55.7% (95% CI, 44.7-66.1). ORR is 87.4%, (95% CI, 78.1-93.2) and bpCR is 35.4% (95% CI, 25.8-46.5). The mean Ki67 expression reduces from 40.4% at baseline to 17.9% (P < 0.001) at time of surgery. The most frequent grade 3 or 4 adverse events are neutropenia, leukopenia, and diarrhoea. There is no serious adverse event- or treatment-related death. This fully oral, chemotherapy-free, triplet combined therapy has the potential to be an alternative neoadjuvant regimen for patients with TPBC.
Disciplines :
Oncology
Author, co-author :
Niu, Nan; Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China ; Innovative Cancer Drug Research and Development Engineering Centre of Liaoning Province, Shenyang, China
Qiu, Fang; Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China ; Innovative Cancer Drug Research and Development Engineering Centre of Liaoning Province, Shenyang, China
Xu, Qianshi ; Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China ; Innovative Cancer Drug Research and Development Engineering Centre of Liaoning Province, Shenyang, China
He, Guijin; Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China ; Innovative Cancer Drug Research and Development Engineering Centre of Liaoning Province, Shenyang, China
Gu, Xi; Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China ; Innovative Cancer Drug Research and Development Engineering Centre of Liaoning Province, Shenyang, China
Guo, Wenbin; Department of Breast Surgery, Dalian Municipal Central Hospital, Affiliated Hospital of Dalian Medical University, Dalian, China
Zhang, Dianlong; Department of Breast Surgery, Affiliated Zhongshan Hospital of Dalian University, Dalian, China
Li, Zhigao ; Department of Breast Surgery, Cancer Hospital of Harbin Medical University, Harbin, China
Zhao, Yi; Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China ; Innovative Cancer Drug Research and Development Engineering Centre of Liaoning Province, Shenyang, China
Li, Yong; Department of Breast Surgery, Benxi Central Hospital, The Fifth Affiliated Hospital of China Medical University, Benxi, China
Li, Ke; Department of Breast Surgery, Anshan Cancer Hospital, Anshan, China
Zhang, Hao; Department of Breast Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China
Zhang, Peili; Department of Breast Surgery, Baotou Cancer Hospital, Baotou, China
Huang, Yuanxi; Department of Breast Surgery, Cancer Hospital of Harbin Medical University, Harbin, China
Zhang, Gangling; Department of Breast Surgery, Baotou Cancer Hospital, Baotou, China
Han, Hongbin; Department of Breast Surgery, Liaohe Oilfield General Hospital, Affiliated Hospital of China Medical University, Panjin, China
Cai, Zhengang; Department of Breast Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian, China
Li, Pengfei; Department of Thoracic and Breast Surgery, Yan'an People's Hospital, Yan'an, China
Xu, Hong; Department of Breast Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China
Chen, Guanglei; Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China ; Innovative Cancer Drug Research and Development Engineering Centre of Liaoning Province, Shenyang, China
Xue, Jinqi; Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China ; Innovative Cancer Drug Research and Development Engineering Centre of Liaoning Province, Shenyang, China
Jiang, Xiaofan; Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China ; Innovative Cancer Drug Research and Development Engineering Centre of Liaoning Province, Shenyang, China
Jahromi, Alireza Hamidian ; Division of Plastic and Reconstructive Surgery, Temple University Medical Center, Philadelphia, PA, USA
Li, Jinshi; Department of Anesthesiology, the First Affiliated Hospital of China Medical University, Shenyang, China
Zhao, Yu; Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN, 55905, USA
de Faria Castro Fleury, Eduardo; Instituto Brasileiro de Controle do Câncer Oncologia (IBCC Oncologia), São Paulo, Brazil
Huo, Shiwen; Jiangsu Hengrui Pharmaceuticals, Shanghai, China
Li, Huajun; Jiangsu Hengrui Pharmaceuticals, Shanghai, China
Jerusalem, Guy ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'oncologie médicale
Tripodi, Domenico ; Department of Surgical Sciences, Sapienza University of Rome, Rome, Italy
Liu, Tong ; Department of Breast Surgery, Cancer Hospital of Harbin Medical University, Harbin, China. liutong@hrbmu.edu.cn
Zheng, Xinyu ; Department of Breast Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China. xyzheng@cmu.edu.cn
Liu, Caigang ; Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China. liucg@sj-hospital.org ; Innovative Cancer Drug Research and Development Engineering Centre of Liaoning Province, Shenyang, China. liucg@sj-hospital.org
Jiangsu Hengrui Pharmaceuticals provided the study drug dalpiciclib free of charge and pyrotinib with a discount for patients enrolled in the study. The drug provider was not involved in the study design, data collection, and analysis as well as the paper writing. We thank the patients, their families, other investigators, and investigational site members involved in this study. We also appreciate the academic support from the AME Breast Cancer Collaborative Group.
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