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Clinical & Experimental Metastasis

, Volume 32, Issue 7, pp 729–737 | Cite as

Activity of T-DM1 in Her2-positive breast cancer brain metastases

  • Rupert Bartsch
  • Anna S. Berghoff
  • Ursula Vogl
  • Margaretha Rudas
  • Elisabeth Bergen
  • Peter Dubsky
  • Karin Dieckmann
  • Katja Pinker
  • Zsuzsanna Bago-Horvath
  • Arik Galid
  • Leopold Oehler
  • Christoph C. Zielinski
  • Michael Gnant
  • Guenther G. Steger
  • Matthias PreusserEmail author
Research Paper

Abstract

Brain metastases (BM) are frequently diagnosed in metastatic Her2-positive breast cancer. Local treatment remains the standard of care but lapatinib plus capecitabine was recently established as systemic therapy option. Due to a disruption of the blood–brain/tumour-barrier at metastatic sites, even large molecules may penetrate into the central nervous system (CNS). Here, we report on the activity of T-DM1 in Her2-positive breast cancer BM. T-DM1 was administered at a dose of 3.6 mg once every 3 weeks as primary systemic therapy for BM or upon documented CNS progression after initial local treatment. Thus, this study allowed for the appraisal of T-DM1 activity in BM. Restaging was conducted every 12 weeks with MRI or whenever symptoms of disease progression occurred. Ten patients were included; in two asymptomatic subjects, T-DM1 was administered as primary therapy, while eight had progressive BM. All patients had received prior treatment with trastuzumab, six had already received lapatinib, and three pertuzumab as well. Three patients had partial remission of BM, and two patient had stable disease lasting for ≥6 months; two further patients had stable disease for <6 months while three progressed despite treatment. At 8.5 months median follow-up, intracranial PFS was 5 months, and median OS from initiation of T-DM1 was not reached. Local treatment of BM remains the standard of care; lapatinib plus capecitabine is currently the best established systemic therapy option. Still, T-DM1 apparently offers relevant clinical activity in BM and further investigation is warranted.

Keywords

Breast cancer Brain metastases Her2 positive T-DM1 Systemic therapy 

Abbreviations

BM

Brain metastases

CNS

Central nervous system

BBB

Blood–brain-barrier

WBRT

Whole brain radiotherapy

ER

Oestrogen-receptor

PgR

Progesterone-receptor

CR

Complete response

PR

Partial response

PD

Progressive disease

PFS

Progression free survival

OS

Overall survival

SD

Stable disease

Notes

Funding

The costs for this project were covered by the research budget of the Department of Medicine I, Medical University of Vienna.

Compliance with ethical standards

Conflicts of interest

Rupert Bartsch: advisory boards: Roche Austria. GlaxoSmithKline; honoraria: GlaxoSmithKline, Roche Austria; research Support: Roche Austria. Anna Sophie Berghoff: travel support Roche. Ursula Vogl: travel grants: Roche. Peter Dubsky: advisory boards: Roche, Pfizer; travel support: Novartis, Astra Zeneca. Christoph C. Zielinski: advisory boards: Roche. Günther Steger: advisory boards, travel support, and honoraria: Hofmann La Roche, Roche Austria. Matthias Preusser: lecture honoraria: GSK, Roche; research support: Roche; advisory boards: Roche. All other authors declare no conflicts of interest.

Supplementary material

10585_2015_9740_MOESM1_ESM.docx (11 kb)
Supplementary material 1 (DOCX 11 kb)

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Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • Rupert Bartsch
    • 1
    • 2
  • Anna S. Berghoff
    • 1
    • 2
  • Ursula Vogl
    • 3
  • Margaretha Rudas
    • 1
    • 4
  • Elisabeth Bergen
    • 1
    • 2
  • Peter Dubsky
    • 1
    • 5
  • Karin Dieckmann
    • 1
    • 6
  • Katja Pinker
    • 1
    • 7
  • Zsuzsanna Bago-Horvath
    • 1
    • 4
  • Arik Galid
    • 8
  • Leopold Oehler
    • 3
  • Christoph C. Zielinski
    • 1
    • 2
  • Michael Gnant
    • 1
    • 5
  • Guenther G. Steger
    • 1
    • 2
  • Matthias Preusser
    • 1
    • 2
    Email author
  1. 1.Comprehensive Cancer Centre ViennaMedical University of ViennaViennaAustria
  2. 2.Department of Medicine I, Clinical Division of Oncology, Comprehensive Cancer Center Vienna, Central Nervous System Unit (CCC-CNS)Medical University of ViennaViennaAustria
  3. 3.Department of MedicineSt. Joseph Hospital, ViennaViennaAustria
  4. 4.Department of PathologyMedical University of ViennaViennaAustria
  5. 5.Department of SurgeryMedical University of ViennaViennaAustria
  6. 6.Department of RadiotherapyMedical University of ViennaViennaAustria
  7. 7.Biomedical Imaging and Image-guided Therapy, Division of Molecular and Gender ImagingMedical University of ViennaViennaAustria
  8. 8.Department of GynaecologyHanusch HospitalViennaAustria

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