Dalpiciclib and pyrotinib in women with HER2-positive advanced breast cancer: a single-arm phase II trial

• Published in: Nature communications Vol. 14; no. 1; p. 6272
• Main Authors: Yan, Min, Niu, Limin, Lv, Huimin, Zhang, Mengwei, Wang, Jing, Liu, Zhenzhen, Chen, Xiuchun, Lu, Zhenduo, Zhang, Chongjian, Zeng, Huiai, Zhao, Shengnan, Feng, Yajing, Sun, Huihui, Li, Huajun
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.10.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 692/308/153; 692/308/2779/109/1941; 692/4028/67/1347; Breast cancer; Cyclin-dependent kinase 4; Diarrhea; ErbB-2 protein; Humanities and Social Sciences; Kinases; Leukocytes (neutrophilic); Metastases; multidisciplinary; Protein-tyrosine kinase; Science; Science (multidisciplinary); Survival; Synergistic effect; Toxicity; Tyrosine
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-41955-7

CDK4/6 inhibitors have shown a synergistic effect with anti-HER2 therapy in hormone receptor (HR)-positive and HER2-positive breast cancer (BC). In this phase 2 study (NCT04293276), we aim to evaluate a dual-oral regimen of CDK4/6 inhibitor dalpiciclib combined with HER2 tyrosine kinase inhibitor pyrotinib as front-line treatment in women with HER2-positive advanced BC ( n  = 41) including those with HR-negative disease. The primary endpoint is the objective response rate, and secondary endpoints include progression-free survival (PFS), overall survival (OS), and safety. With a median follow-up of 25.9 months, 70% (28/40) of assessable patients have a confirmed objective response, meeting the primary endpoint. The median PFS is 11.0 months (95% CI = 7.3–19.3), and OS data are not mature. The most common grade 3 or 4 treatment-related adverse events (AEs) are decreased white blood cell count (68.3%), decreased neutrophil count (65.9%), and diarrhea (22.0%). Most AEs are manageable, and no treatment-related deaths occur. These findings suggest that this combination may have promising activity and manageable toxicity. Further investigation is needed. Dalpiciclib is a CDK4/6 inhibitor, recently approved for treatment in advanced breast cancer patients in China. Here, the authors report the results of a phase II trial investigating oral dalpiciclib (CDK4/6 inhibitor) and pyrotinib (pan-HER inhibitor) in patients with HER2-positive metastatic breast cancer.