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

• Published in: Nature communications Vol. 13; no. 1; pp. 7043 - 9
• 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: Journal Article Web Resource
• Language: English
• Published: London Nature Publishing Group UK 17.11.2022; Nature Publishing Group; Nature Research; Nature Portfolio
• 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  < 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. Neoadjuvant therapy is recommended for patients with locally advanced breast cancer. Here the authors report the results of a phase 2 clinical trial of oral neoadjuvant therapy with pyrotinib (pan-HER tyrosine kinase inhibitor), letrozole (aromatase inhibitor) and dalpiciclib (CDK4/6 inhibitor) in patients with treatment-naïve and stage II-III triple positive breast cancer.