Real-world outcomes in patients with brain metastases secondary to HER2-positive breast cancer: An Australian multi-centre registry-based study

Abstract

Background: Brain metastases are common in HER2-positive breast cancer and associated with a poorer prognosis. The advent of HER2-targeted treatment has improved survival in HER2-positive metastatic breast cancer (MBC)overall, whereas the benefit in patients with brain metastases is unclear. This study aims to explore realworld outcomes of patients with brain metastases in HER2-positive MBC. Method(s): Data was extracted from the Treatment of Advanced Breast Cancer in the HER2-Positive Australian Patient (TABITHA), a prospective registry collecting patient data from 16 Australian sites diagnosed between 2015 and 2020. Data analysed include treatment of brain metastases and survival outcomes. Result(s): We identified that 131 (38%) of 346 patients with HER2- positive MBC had brain metastases during their clinical course, including 44 (34%) with brain metastases at diagnosis. Sixty-two (47%) had >=4 brain metastases, and 10 (8%) had leptomeningeal involvement. Receipt of prior adjuvant HER2-targeted treatment versus no adjuvant treatment did not impact on the incidence of brain metastases (48% vs. 34%, p = 0.06). Twenty-one patients (16%) received initial surgical resection. One hundred five patients (80%) received radiation therapy for brain metastases, of which 40 (38%) received stereotactic radiotherapy. Ninety-one patients (70%) received first-line therapy with pertuzumab and trastuzumab, whilst six (4.7%) received T-DM1. Only six (5%) patients did not receive HER2-targeted therapy in any line of treatment. Median overall survival was 96months in those without brain metastases, 38 months longer than those with brain metastases at diagnosis (p = 0.02). Conclusion(s): In this Australian first registry-based study, we found a high uptake of HER2-targeted therapy in patients with brain metastases in HER2-positive MBC. In line with historical data, patients with brain metastases continue to have poorer prognosis. Given that many clinical trials exclude patients with brain metastases, clinical trials focused on patients with brain metastases should be pursued in the era of new HER2 therapies in MBC.