Abstract P2-20-05: Systemic bevacizumab, etoposide and cisplatin (the BEEP regimen) improves the survival of leptomeningeal metastasis of breast cancer
Authors: Chen Tom Wei-Wu , Jan I-Shiow , Chang Dwang-Ying , Lin Ching-Hung , Chen I-Chun , Chen Ho-Min , Cheng Ann-Lii , Lu Yen-Shen 
Published: March 2020

Abstract
Introduction: Leptomeningeal metastasis (LM) of breast cancer (BC) is dismal with median overall survival (OS) around 3-4 months. Newer therapies such as bevacizumab, etoposide, cisplatin (BEEP) or intrathecal (IT) trastuzumab have shown the activity in in LM (BMC Cancer. 2015 Apr 17;15(1):299). From 2014, we actively provide the treatment choice of BEEP for patients with leptomeningeal metastases in National Taiwan University Hospital (NTUH). We aim to report and analyze the successful experience of BEEP treatment for breast cancer LM patients in the recent years.
Methods: We extracted the patient list from the cytology laboratory of NTUH for every BC patient who was diagnosed as cerebrospinal fluid (CSF) cytology positive LM in NTUH from 2011 to 2016. Medical records of anticancer treatment modality before and after the diagnosis of cytology confirmed LM were summarized. The main treatment efficacy outcome is OS, defined as the date from confirmed positive CSF cytology for carcinoma cells to the date of death. In order to understand the effect of actively providing BEEP treatment, the patients were also divided into two diagnostic time periods: 2011-2013 vs 2014-2016. Univariate and multivariate analyses were performed to understand the prognostic factors for the whole group.
Results: From 2011 to 2016, a total of 34 consecutive patients with cytology confirmed LM were identified. The median age at the time of LM diagnosis was 57 (range 30-80). The treatment after LM diagnosis included: intrathecal (IT) methotrexate (MTX) (82.4%), systemic chemotherapy (68%; BEEP regimen n =19, others n = 3), and WBRT (n = 5, 14.7%). For HER2-positive patients, 43 % (n = 3) also received IT trastuzumab. OS improved over diagnostic time periods 2014-2016 vs 2011-2013 (13.57 vs 3.20 months, p = 0.0036), where 7 of 17 (41%) and 12 of 17 (71%) patients received BEEP treatment, respectively. When all treatments were included in the multivariate model, BEEP (HR 0.24, p=0.0032) and IT trastuzumab (HR 0.22, p = 0.035) but not IT MTX (HR 0.86, p = 0.78) remained significant prognostic factors (Table 1). The CSF response (as defined by two consecutive negative CSF cytology results) was 58% (19/34) with a median of 28 days from treatment to CSF response. Patients with a CFS response is associated with significant better OS (HR 0.25, p &lt; 0.001).
Conclusion: We have shown that MBC LM is a treatable disease and systemic BEEP and IT trastuzumab are efficacious treatments that could improve survival.
Table 1. Adjusted hazard ratios of treatments for leptomeningeal metastasis in 34 patientsAdjusted hazard ratio (95% CI)p-valueIntrathecal methotrexate vs non-intrathecal methotrexate0.86 (0.28, 2.64)0.787BEEP vs non-BEEP0.24 (0.09, 0.62)0.003Intrathecal trastuzumab vs no intrathecal trastuzumab0.22 (0.05, 0.90)0.035
Citation Format: Tom Wei-Wu Chen, I-Shiow Jan, Dwang-Ying Chang, Ching-Hung Lin, I-Chun Chen, Ho-Min Chen, Ann-Lii Cheng, Yen-Shen Lu. Systemic bevacizumab, etoposide and cisplatin (the BEEP regimen) improves the survival of leptomeningeal metastasis of breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-20-05.