Systemic treatment of breast cancer with leptomeningeal metastases using bevacizumab, etoposide and cisplatin (BEEP regimen) significantly improves overall survival

J Neurooncol. 2020 May;148(1):165-172. doi: 10.1007/s11060-020-03510-y. Epub 2020 Apr 29.

Abstract

Introduction: Metastatic breast cancer (MBC) with leptomeningeal metastases (LM) has dismal survival. We aim to determine if modern systemic therapy, especially the bevacizumab, cisplatin, and etoposide (BEEP) regimen, is beneficial to MBC LM patients.

Methods: We excerpted data from a prospectively collected cytopathology database for MBC patients who were diagnosed with LM by positive cerebrospinal fluid cytology. The primary outcome was OS from cytologically confirmed LM until death. Univariate and multivariate analyses were performed to elucidate prognostic factors.

Results: We identified 34 patients with cytologically confirmed LM. Treatments after LM diagnosis included: intrathecal methotrexate (82.4%), systemic chemotherapy (68%; BEEP n = 19, others n = 4), and whole brain radiotherapy (n = 5, 14.7%). Three of seven HER2-positive patients (43%) also received intrathecal trastuzumab. OS was improved in 2014-2016 compared with 2011-2013 (13.57 vs 3.20 months, p = 0.004), when 12/17 (71%) versus 7/17 (41%) patients received BEEP, respectively. In the multivariate model including all treatments, BEEP (HR 0.24, p = 0.003) and intrathecal trastuzumab (HR 0.22, p = 0.035), but not intrathecal methotrexate (HR 0.86, p = 0.78), remained significant prognostic factors.

Conclusions: MBC with LM is treatable-systemic BEEP are efficacious and may improve survival.

Keywords: Bevacizumab; Breast cancer; Chemotherapy; Intrathecal therapy; Leptomeningeal metastasis; Trastuzumab.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bevacizumab / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cisplatin / therapeutic use*
  • Etoposide / therapeutic use*
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Meningeal Neoplasms / drug therapy*
  • Meningeal Neoplasms / secondary
  • Middle Aged
  • Prospective Studies
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Bevacizumab
  • Etoposide
  • Cisplatin