2017_SBRT_Course Book

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

Ruper t Bar tsch 1,2 Elisabeth Bergen 1,2

• Anna S. Berghoff 1,2

• Ur sula Vogl 3

• Margaretha Rudas 1,4 •

• 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 al copy

Author'spersonal copy

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 Best i tracranial response CR PR SD PD Cranial Clinical Benefit Rate (CBR) Best extracranial response N = 10 N 0 3 4 3 5

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. N = 10 N % 0 0.0 3 30.0 4 40.0 Clin Exp Metastasis

Clin Exp Metastasis

%

0.0

30.0

40.0

30.0

3

30.0

50.0

Keywor ds Breast cancer Brain metastases Her2 positive T-DM1 Systemic therapy 50.0 5