Efficacy and safety of pyrotinib combined with albumin‐bound paclitaxel as first‐line treatment for HER2‐positive metastatic breast cancer in patients previously treated with adjuvant and/or neoadjuvant trastuzumab therapy: The stage 1 results of a single‐arm, phase 2 prospective clinical trial

• Published in: Clinical and translational medicine Vol. 14; no. 5; pp. e1687 - n/a
• Main Authors: Man, Xiaochu, Huang, Jie, Sun, Shujuan, Zhou, Dongdong, Zhang, Baoxuan, Fang, Shu, Zheng, Fangchao, Li, Chao, Wang, Xinzhao, Huang, Wei, Wang, Linlin, He, Qingqing, Fu, Hui, Zhang, Yan, Liu, Changrui, Dong, Lin, Zhao, Xianguang, Xu, Liang, Sun, Xiao, Fan, Bingjie, Song, Lihua, Zhou, Zhengbo, Yu, Jinming, Li, Huihui
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.05.2024; John Wiley and Sons Inc; Wiley
• Subjects: Acrylamides - therapeutic use; Adult; Aged; Albumin-Bound Paclitaxel - pharmacology; Albumin-Bound Paclitaxel - therapeutic use; albumin‐bound paclitaxel; Aminoquinolines - pharmacology; Aminoquinolines - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Breast cancer; Breast Neoplasms - drug therapy; Cancer therapies; Chemotherapy; Clinical trials; Consent; Female; HER2‐positive metastatic breast cancer; Humans; Kinases; Medical prognosis; Metastasis; Middle Aged; Monoclonal antibodies; Neoadjuvant Therapy - methods; Olink; Oncology; Patients; Prospective Studies; Proteins; Proteomics; Proto-Oncogene Mas; Pyrotinib; Receptor, ErbB-2 - metabolism; Sulfinic Acids - pharmacology; Sulfinic Acids - therapeutic use; Targeted cancer therapy; Trastuzumab - pharmacology; Trastuzumab - therapeutic use; Treatment Outcome; Pyrotinib; Olink; HER2‐positive metastatic breast cancer; albumin‐bound paclitaxel
• ISSN: 2001-1326; 2001-1326
• DOI: 10.1002/ctm2.1687

Objective It has been observed that the prognosis of patients with HER2‐positive metastatic breast cancer has improved significantly with HER2‐targeted agents. However, there is still a lack of evidence regarding first‐line anti‐HER2 treatment options for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2‐positive metastatic breast cancer. Besides, there are no reliable markers that can predict the efficacy of anti‐HER2 treatment in these patients. Methods Patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2‐positive metastatic breast cancer were enrolled. Pyrotinib plus albumin‐bound paclitaxel were used as first‐line treatment. The primary endpoint was the objective response rate (ORR). The safety profile was also assessed. In order to explore predictive biomarkers using Olink technology, blood samples were collected dynamically. Results From December 2019 to August 2023, the first stage of the study involved 27 eligible patients. It has not yet reached the median PFS despite the median follow‐up being 17.8 months. Efficacy evaluation showed that the ORR was 92.6%, and the DCR was 100%. Adverse events of grade 3 or higher included diarrhoea (29.6%), leukopenia (11.1%), neutropenia (25.9%), oral mucositis (3.7%), and hand‐foot syndrome (3.7%). Toll‐like receptor 3 (TLR3) and Proto‐oncogene tyrosine‐protein kinase receptor (RET) were proteins with significant relevance to PFS in these patients. Conclusions This study demonstrates that pyrotinib plus albumin‐bound paclitaxel as a first‐line treatment regimen shows good efficacy and manageable safety for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2‐positive metastatic breast cancer. Besides, a significant association was identified between the expression levels of TLR3 and RET and the PFS in patients. The combination of pyrotinib and albumin‐bound paclitaxel as a first‐line treatment regimen delivers favorable efficacy with manageable safety in patients with HER2‐positive metastatic breast cancer who have previously received adjuvant and/or neoadjuvant trastuzumab therapy. And TLR3 and RET might serve as potential predictive proteins for progression‐free survival in these patients.