Abstract P1-14-03: Efficacy and Safety of Pyrotinib-Based Therapy in the Treatment of HER2-positive Breast Cancer Patients with Brain Metastases:A Multi-Center Real-World Study

Abstract Background: An estimated 30-50% of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) will develop brain metastases (BMs), and there are few effective treatment options. Pyrotinib has shown good efficacy in HER2-positive breast cancer patients with BMs in a single-arm phase II trial, but there is a lack of data from randomized controlled trial and real-world study. The purpose of this multi-center real-world study was to evaluate the efficacy and safety of pyrotinib-based therapy in HER2-positive breast cancer patients with BMs in real world. Methods: We reviewed the data of HER2-positive breast cancer patients with BMs who were treated with pyrotinib-based therapy from January 2018 to September 2021 at Shandong Cancer Hospital and Institute and other hospitals in Shandong Province in China. The initial dose of pyrotinib in most patients (n=92, 85.2%) was 400 mg once a day for every 21 days as a cycle. All patients were evaluated for tumor response every two cycles according to RECIST 1.1. The primary endpoint was progression free survival (PFS) and secondary endpoints were compounded objective response rate (ORR) and CNS-ORR (the ORR of central nervous system), compounded disease control rate (DCR) and CNS-DCR (the DCR of central nervous system) and overall survival (OS). The safety profile has also been assessed. The updated graded prognostic assessment for breast cancer patients with brain metastases (Breast GPA) includes age, Karnofsky performance status (KPS), extracranial metastases, number of brain metastases, and tumor subtype. It is divided into four subgroups (0-1.0, 1.5-2.0, 2.5-3.0 and 3.5-4.0) with different prognosis (the median survival: 6 months, 12.9 months, 23.5 months, and 36.3 months). Results: 101 patients were assessed for efficacy and toxicity. The median PFS is 10.0 months (95% CI, 6.9 to 13.1 months), and OS data were not available at the time of analysis. In overall patients, patients with GPA of 0-2.0 achieved shorter PFS (4.8 months vs 12.4 months, P=0.003). Trastuzumab (neo and adjuvant) (P=0.021), local therapy for BMs (P﹤0.001) and pyrotinib treatment (P=0.022) had significant positive correlation with PFS. In patients with GPA of 0-2.0, the median PFS of different local treatment methods was significantly different (P﹤0.001), stereotactic radiotherapy alone (13.6 months) was better than whole-brain radiotherapy alone (4.8 months) and combined local therapy (6.7 months); patients who received pyrotinib first in the BMs stage had longer PFS than those who did not (6.7 months vs 2.7 months, P=0.009) and radiotherapy for BMs (P=0.036) had correlation with longer PFS. Cox multivariate analysis indicated that GPA (0-2.0 vs 2.5-4.0) was independent predictor of PFS. For overall patients, the ORR was 42.6% and DCR was 88.1%. The CNS-ORR was 45.5% and CNS-DCR was 90.1%. Diarrhea (71.3%) was the most common adverse events (AEs), 47 patients (46.5%) reported grade 1-2 diarrhea, 25 patients (24.8%) reported grade 3 diarrhea. In addition, the more common AEs of grade 3 were loss of appetite (7.9%), hand-foot syndrome (6.9%), nausea (5.9%) and vomiting (5.0%). No grade 4 and 5 AEs occurred. Conclusions: Pyrotinib-based therapy is effective and tolerable in HER2-positive breast cancer patients with BMs. In the subgroup with Breast GPA 0-2.0, patients treated with radiotherapy had a better prognosis, and stereotactic radiosurgery alone was a viable option. Clinical trial information: ChiCTR2000037995. Citation Format: Huihui Li, Jie Huang, Qiaorui Tan, Xiaochu Man, Sha Yin, Shujuan Sun, Yu Hu, Wenhuan Li, Dongdong Zhou, Lihua Song, Baoxuan Zhang, Liang Xu, Xinzhao Wang, Xuemei Xie. Efficacy and safety of pyrotinib-based therapy in the treatment of HER2-positive breast cancer patients with brain metastases:a multi-center real-world study [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 P1-14-03.