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Activity of T-DM1 in Her2-positive breast cancer brain metastases
Ruper t Bar tsch
1,2
•
Anna S. Berghoff
1,2
•
Ur sula Vogl
3
•
Margaretha Rudas
1,4
•
Elisabeth Bergen
1,2
•
Peter Dubsky
1,5
•
Kar in Dieckmann
1,6
•
Katj a Pinker
1,7
•
Zsuzsanna Bago-Hor vath
1,4
•
Ar ik Galid
8
•
Leopold Oehler
3
•
Chr istoph C. Zielinski
1,2
•
Michael Gnant
1,5
•
Guenther G. Steger
1,2
•
Matthias Preusser
1,2
Received: 11 June 2015 / Accepted: 21 August 2015
Ó Springer Science+Business Media Dordrecht 2015
Abstract Brain metastases (BM) are frequently diag-
nosed in metastatic Her2-positive breast cancer. Local
treatment remains the standard of care but lapatinib plus
capecitabine was recently establ ished as systemic therapy
option. Due to a disruption of the blood–brain/tumour-
barrier at metastatic sites, even large molecules may pen-
etrate 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 C6 months; two fur-
ther patients had stable disease for \ 6 months while three
progressed despite treatment. At 8.5 months median fol-
low-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 cape-
citabine is currently the best established systemic therapy
option. Still, T-DM1 apparently offers relevant clinical
activity in BM and further investigation is warranted.
Keywor ds Breast cancer Brain metastases Her2
positive T-DM1 Systemic therapy
N = 10
N
%
Best i tracranial response
CR
0
0.0
PR
3
30.0
SD
4
40.0
PD
3
30.0
Cranial Clinical Benefit Rate (CBR)
5
50.0
Best extracranial response
Clin Exp Metastasis
Author'spersonal copy
N = 10
N
%
0
0.0
3
30.0
4
40.0
3
30.0
5
50.0
Clin Exp Metastasis
al copy