404 - Intrathecal trastuzumab in the treatment of leptomeningeal metastases from HER2-positive cancer

Date 28 September 2012
Event ESMO Congress 2012
Session Publication Only
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Metastatic
Presenter Daniel Machado
Authors D. Machado1, M. Oliveira2, S. Esteves3, T. Marques4, A. Clara4, M. Brito4, J. Freire4, J. Bravo Marques5, A. Moreira4
  • 1Portuguese Institute of Oncology, Lisbon/PT
  • 2Breast Cancer Group, Vall d'Hebron Institut d'Oncologia, Barcelona/ES
  • 3Clinical Investigation Unit, Portuguese Institute of Oncology, Lisbon/PT
  • 4Medical Oncology, Portuguese Institute of Oncology, Lisbon/PT
  • 5Neuro-oncology, Portuguese Oncology Insitute, Lisbon/PT

Abstract

Introduction

Up to 8% of all cancer patients develop leptomeningeal metastases (LM). Median overall survival after diagnosis is approximately 1 month. Trastuzumab, a monoclonal antibody against the HER2 receptor, is used in the treatment of HER2 positive cancer patients. It is still not clear if systemic trastuzumab can penetrate the intact blood brain barrier, because of its high molecular weight. Given intrathecally, trastuzumab could achieve higher concentrations in the cerebrospinal fluid (CSF).

Purpose

Determine safety, response and overall survival of patients treated with intrathecal (IT) trastuzumab, in a single centre population.

Patients and methods

Clinical data of patients treated with IT trastuzumab have been reviewed. Survival was defined as time since beginning of IT trastuzumab until death or last follow-up.

Results

A total of 4 patients have been treated with IT trastuzumab (Table 1). Table 1. Patient characteristics, previous treatment and survival.

Table: 404

Patient Sex Age Primary tumor Histology Previous treatment Survival (months)
A F 41 breast IDC, HR- CT, S, RT, sT 1,6 +
B F 44 breast IDC, HR+ CT, RT, HT, S, sT 23,7
C F 31 breast IDC, HR+ S, RT, HT, sT 2,4
D M 58 stomach ADC CT, S 1
.

All HER2 positive, IDC invasive ductal carcinoma, ADC adenocarcinoma, S surgery, RT radiotherapy, HT hormonal treatment, sT systemic trastuzumab. LM were confirmed by lumbar puncture in patients B, C and D. In patient A LM were diagnosed by MRI (CSF cytology persistently negative). Patients A, B, and C received weekly IT trastuzumab 25 mg. Patient D received weekly IT (trastuzumab 25 mg + methotrexate 12 mg). Toxicity related to IT trastuzumab was not observed. The CSF cytology remained positive in patient D and became negative after 1 and 3 weeks for patient C and B, respectively. Patient A was still receiving treatment at last follow-up.

Conclusions

In our group of patients, IT trastuzumab was well tolerated and had encouraging results. Ours is a small and somewhat heterogeneous population and we can not extrapolate on the efficacy of trastuzumab in this setting, but a study with a larger number of patients is warranted and may help identify patients appropriate for this therapy.

Disclosure

All authors have declared no conflicts of interest.