Clinical outcomes of breast leptomeningeal disease treated with intrathecal trastuzumab, intrathecal chemotherapy, or whole brain radiation therapy.

Abstract

PURPOSE:

Leptomeningeal disease is a rare presentation of advanced metastatic breast cancer. The purpose of this study was to evaluate craniospinal progression between intrathecal (IT) trastuzumab, IT chemotherapy, and whole brain radiation therapy (WBRT) in leptomeningeal disease.

METHODS:

A total of 56 patients were identified with breast cancer leptomeningeal disease at our institution treated with IT trastuzumab (n = 18; 32%), single-agent IT chemotherapy (methotrexate n = 14 or thiotepa n = 1; 27%), or WBRT alone (n = 23; 41%). Patients were treated beginning November 2012 and followed until November 2018.

RESULTS:

Median time from breast cancer diagnosis to development of leptomeningeal disease was 4.3 years. There were no significant differences noted between IT trastuzumab, IT chemotherapy, or WBRT groups in age (p = 0.4), Karnofsky Performance Status (KPS) (p = 0.07), or receipt of systemic therapy at time of leptomeningeal disease treatment (p = 0.47). Median follow-up of patients from leptomeningeal diagnosis was 5 months (range 0.2-81.1 months). Significant differences were noted in Kaplan-Meier (KM) craniospinal progression-free survival (CS-PFS) with 6-month rates of 44%, 18%, and 26% (p = 0.04) between IT trastuzumab, IT chemotherapy, and WBRT, respectively. Craniospinal control > 10 months was achieved in four patients treated with IT trastuzumab. Twelve-month KM OS rates were 54%, 10%, and 19% (p = 0.01) between IT trastuzumab, IT chemotherapy, and WBRT groups, respectively. IT therapy was adequately tolerated with three patients undergoing treatment-related hospitalizations.

CONCLUSIONS:

In our institutional series, significant differences were noted in CS-PFS and OS by treatment modality. IT trastuzumab should be considered in the management HER2+ breast leptomeningeal disease.

• Authors: Nicholas B Figura, Victoria T Rizk, Homan Mohammadi, Brittany Evernden, Sepideh Mokhtari, H Michael Yu, Timothy J Robinson, Arnold B Etame, Nam D Tran, James Liu, Iman Washington, Roberto Diaz, Brian J Czerniecki, Hatem Soliman, Hyo S Han, Solmaz Sahebjam, Peter A Forsyth, Kamran A Ahmed
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 175 Issue 3 Pg. 781-788 (Jun 2019) ISSN: 1573-7217 [Electronic] Netherlands
• PMID: 30859348 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Thiotepa
• Trastuzumab
• Methotrexate

Topics

• Adult
• Aged
• Breast Neoplasms (therapy)
• Cranial Irradiation (methods)
• Drug Therapy (methods)
• Female
• Hospitalization
• Humans
• Injections, Spinal
• Karnofsky Performance Status
• Meningeal Neoplasms (secondary, therapy)
• Methotrexate (administration & dosage, therapeutic use)
• Middle Aged
• Retrospective Studies
• Survival Analysis
• Thiotepa (administration & dosage, therapeutic use)
• Trastuzumab (administration & dosage, therapeutic use)
• Treatment Outcome