Efficacy and safety of HER2-ADC SHR-A1811 in HER2-positive breast cancer with brain metastases.

作者：Min Yan, Huimin Lv, Limin Niu, Mengwei Zhang, Zhenzhen Liu, Huihui Sun, Jing Wang, Huiai Zeng, Shengnan Zhao, Yajing Feng, Yaowen Cui, Ruoyu Huang · 发表于：Journal of Clinical Oncology · 年份：2024 · DOI：10.1200/jco.2024.42.16_suppl.e13006 · 被引用次数：5 · 研究领域：HER2/EGFR in Cancer Research、Radiopharmaceutical Chemistry and Applications、Cancer Treatment and Pharmacology

e13006 Background: A substantial proportion of patients with HER2-positive (HER2+) breast cancer would develop brain metastases. Systemic HER2-target therapy is a viable option for these patients. The new generation of HER2-directed antibody-drug conjugate (ADCs) has significantly altered the treatment landscape for breast cancer and has demonstrated promising results in patients with breast cancer brain metastases (BCBM). Therefore, we conducted a prospective, multi-arm, multi-cohort, phase 2 trial (NCT05769010) to evaluate the use of a novel HER2-target ADC SHR-A1811 in HER2-expressing BCBM. Methods: Patients with radiotherapy-naïve HER2-expressing BCBM, and not in need of immediate local treatment were enrolled, and they received SHR-A1811 as monotherapy (Arm 1 HER2+ and Arm 4 HER2-low) or in combination with pyrotinib or bevacizumab (Arm 2 and Arm 3 HER2+) until disease progression, unaccepted toxicity, or no further benefit. Here we present the interim results of Arm 1 consisted of HER2+ patients treated with SHR-A1811. Patients were required to have at least one measurable lesion as defined by RANO-BM criteria. Previous HER2-targeted treatments, chemotherapies, and endocrine therapies were allowed. The primary endpoint was the intracranial overall response rate (ORR-IC) according to RANO-BM. Key secondary endpoints included the overall response rate as per RECIST 1.1, progression-free survival, overall survival, and safety. Results: Between March 31, 2023, and November ...