Abstract OT3-29-01: A Phase Ib/II Study of anlotinib combined with pyrotinib and capecitabine for HER2-Positive Metastatic Breast Cancer
Authors: Luo Ting , Zhong Xiaorong , Chen Jie 
Published: March 2023

Abstract
Background: Preclinical data showed that high levels of vascular endothelial growth factor (VEGF) may lead to aggressive behavior in breast tumors that overexpress HER2. AVEREL study demonstrated that bevacizumab in combination with trastuzumab and docetaxel as first-line treatment increased progression-free survival (PFS) in HER2 postive metastatic breast cancer (BC) patients (BTH vs TH:16.5m vs 13.7m, HR=0.82, P=0.0775). It is necessary to exploring new effective and tolerable strategy of targeting both HER2 signaling and angiogenesis. PHENIX and PHOEBE studies proved pyrotinib (an irreversible pan-ErbB receptor tyrosine kinase inhibitor) plus capecitabine improved prognosis for patients with advanced HER2 positive BC. Anlotinib is a novel multi-target tyrosine kinase inhibitor that effectively inhibits VEGFR, FGFR, c-KIT, c-MET and RET. This study is aimed to evaluate safety, tolerability and efficacy of anlotinib combined with pyrotinib and capecitabine for HER2-Positive metastatic BC. Methods: This open-label study is designed to include patients with pathologically confirmed HER2-positive metastatic breast cancer that have progressed or relapsed after treatment with trastuzumab or inability to receive trastuzumab in West China Hospital, Sichuan University. Eligible patients have at least one measurable lesion according to RECIST v1.1; previously received taxanes regimen and had ≤2 line of chemotherapy for advanced disease; an ECOG performance status of 0-1; adequate organ function. In the “3+3” dose-exploring phase, pyrotinib and capecitabine are given at a fixed dose of 400mg qd and 1000 mg/m2 bid respectively. Anlotinib is initially given at a dose of 10mg/d (Level I). If the initial dose level could be tolerated, subsequent patients are assigned to the higher level (Level H) with anlotinib 12mg/d; otherwise, to Level L with anlotinib 8 mg/d. Primary endpoints of phase Ib are dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), safety and efficacy. Phase II is an expansion cohort at the recommended phase II dose (RP2D). The primary endpoint for phase II is one-year PFS rate by investigator-assessed, and secondary endpoints include PFS, overall response rate (ORR), clinical benefit rate (CBR), duration of response (DoR), overall survival (OS) and quality of life. A sample size of 23 provided 80% power at 2-sided alpha = 0.20 to detect a minimum of 20% improvement (45% vs. 65%) in one-year PFS. The phase Ib portion of the trial is currently enrolling in China. Clinical trial information: ChiCTR2100045962. Funding: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Citation Format: Ting Luo, Xiaorong Zhong, Jie Chen. A Phase Ib/II Study of anlotinib combined with pyrotinib and capecitabine for HER2-Positive Metastatic Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT3-29-01.