A multicentre single arm phase 2 trial of neoadjuvant pyrotinib and letrozole plus dalpiciclib for triple-positive breast cancer

• Published in: Nature communications 2022-11, Vol.13 (1), p.7043-9, Article 7043
• Main Authors: Niu, Nan, Qiu, Fang, Xu, Qianshi, He, Guijin, Gu, Xi, Guo, Wenbin, Zhang, Dianlong, Li, Zhigao, Zhao, Yi, Li, Yong, Li, Ke, Zhang, Hao, Zhang, Peili, Huang, Yuanxi, Zhang, Gangling, Han, Hongbin, Cai, Zhengang, Li, Pengfei, Xu, Hong, Chen, Guanglei, Xue, Jinqi, Jiang, Xiaofan, Jahromi, Alireza Hamidian, Li, Jinshi, Zhao, Yu, de Faria Castro Fleury, Eduardo, Huo, Shiwen, Li, Huajun, Jerusalem, Guy, Tripodi, Domenico, Liu, Tong, Zheng, Xinyu, Liu, Caigang
• Format: Article
• Language: English
• Subjects: 101/28; 631/67/1347; 692/700/565/1436/1437; 9/25; Adverse events; Antineoplastic Combined Chemotherapy Protocols; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Aromatase; Biochemistry, Genetics and Molecular Biology (all); Breast cancer; Breast Neoplasms; Breast Neoplasms - pathology; Cancer therapies; Chemistry (all); Chemotherapy; Cyclin-dependent kinase 4; Diarrhea; Effectiveness; Enzyme inhibitors; ErbB-2 protein; Female; General Biochemistry, Genetics and Molecular Biology; General Chemistry; General Physics and Astronomy; Human health sciences; Humanities and Social Sciences; Humans; Ki-67 Antigen; Kinases; Letrozole; Letrozole - therapeutic use; Leukopenia; Multidisciplinary; Neoadjuvant Therapy; Neoadjuvant Therapy - methods; Neutropenia; Oncologie; Oncology; Patients; Physics and Astronomy (all); Protein Kinase Inhibitors; Protein Kinase Inhibitors - therapeutic use; Protein-tyrosine kinase; pyrotinib; Receptor, ErbB-2; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - metabolism; Safety; Science; Science (multidisciplinary); Sciences de la santé humaine; Surgery; Tyrosine
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-34838-w

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