Pyrotinib with trastuzumab and aromatase inhibitors as first-line treatment for HER2 positive and hormone receptor positive metastatic or locally advanced breast cancer: study protocol of a randomized controlled trial
Changjun Wang, Yan Lin, Yidong Zhou, Feng Mao, Hanjiang Zhu, Jinghong Guan, Xiaohui Zhang, Songjie Shen, Xin Huang, Chang Chen, Ru Yao, Jialin Zhao, Qiang Sun
Abstract
BACKGROUND: HER2 dual-blockade combined with aromatase inhibitors (AI) is a promising strategy to improve progression-free survival (PFS) in hormone receptor (HR) positive, metastatic breast cancer (MBC). Pyrotinib is a novel irreversible epidermal growth factor receptor/HER2 dual tyrosine kinase inhibitor. However, there is scarcity of data on the effectiveness and safety of pyrotinib combined with trastuzumab and AI as first-line treatment in a metastatic setting. METHODS/DESIGN: The present study is a prospective, randomized, open-label trial. 198 patients with HER2+/HR+ MBC will be recruited. Eligible patients will be allocated (2:1) to either an experimental group (pyrotinib + trastuzumab + AI) or a control group (trastuzumab + AI). Allocation will be stratified by 1) time since adjuvant hormone therapy (≤ 12 months/> 12 months/no prior hormone therapy); 2) lesion sites (visceral / non-visceral). The primary endpoint is PFS. DISCUSSION: To our knowledge, this is the first prospective randomized controlled trial to assess dual HER2-blockade with pyrotinib in the metastatic setting. This study will provide valuable evidence regarding the efficacy and safety of pyrotinib when combined with trastuzumab and an AI as first-line treatment for MBC. Moreover, it will also evaluate the feasibility of endocrine therapy as an alternative to chemotherapy in providing de-escalation therapy with less toxicity for advanced HR+/HER2+ patients. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03910712 . Registered on 10 Apr. 2019.