Abstract P6-16-10: Activity of T-DM1 in HER2-positive breast cancer brain metastases
Authors: Bartsch Rupert , Berghoff Anna S , Vogl Ursula , Rudas Margaretha , Bergen Elisabeth , Gnant Michael , Dieckmann Karin , Pinker Katja , Bago-Horvath Zsuzsanna , Galid Arik , Oehler Leopold , Zielinksi Christoph C , Steger Guenther G , Preusser Matthias 
Published: May 2015

Abstract
Background
Different local therapy options such as radiotherapy, radiosurgery and neurosurgery remain the mainstay of brain metastases (BM) management, especially in case of oligometastatic or symptomatic disease. Recently, the LANDSCAPE study established lapatinib plus capecitabine (LapCap) as potential standard option for primary systemic treatment in oligosymptomatic patients (pts) with multiple Her2-positive BM. Limited evidence exists with regards to the potential activity of antibodies in BM. Due to a disruption of the blood-brain-barrier at the metastatic site, it is anticipated that even large molecules such as antibodies may penetrate into the central-nervous system (CNS). On the other hand, the CNS is an immune-privileged organ which may hamper activity of trastuzumab. This problem may be overcome by the use of T-DM1.
T-DM1 is an antibody-drug conjugate linking trastuzumab (T) to an anti-microtubule agent providing higher activity and lower toxicity as compared to LapCap. Here, we investigated the activity of T-DM1 in newly diagnosed or progressive BM.
Patients and Methods
Nine pts (median age 55 years) with Her2-positive BM treated at two Austrian centres were included. All pts had received prior treatment with T, five pts (55.6%) had already received lapatinib, and two pts (22.2%) pertuzumab as well.
In two asymptomatic pts, T-DM1 was administered as primary therapy, while seven pts had documented CNS progression upon prior local treatment. T-DM1 was administered every three weeks at a dose of 3.6 mg/kg. Restaging was conducted every twelve weeks with MRI or whenever symptoms of disease progression occurred.
Results
Median follow-up was 6 months and median brain metastases-free survival 11 months. Seven pts (two with primary treatment and five receiving T-DM1 upon CNS progression) are currently assessable for CNS response. 3/7 pts (42.9%) had partial remission, one patient progressing upon prior local therapy had stable disease lasting for 10 months, and one patient had stable disease for 5 month. One patient progressing of prior WBRT had minor response of BM on MRI but no reduction of brain oedema and increasing cortisol doses and was therefore deemed PD. The other patient with primary PD was also progressing after WBRT.
Conclusion
This prospectively sampled case series again indicates that systemic therapy offers activity in Her2-positive BM. LapCap remains the standard of care but T-DM1 offers relevant clinical activity and should be investigated within the context of larger clinical studies.
Citation Format: Rupert Bartsch, Anna S Berghoff, Ursula Vogl, Margaretha Rudas, Elisabeth Bergen, Michael Gnant, Karin Dieckmann, Katja Pinker, Zsuzsanna Bago-Horvath, Arik Galid, Leopold Oehler, Christoph C Zielinksi, Guenther G Steger, Matthias Preusser. Activity of T-DM1 in HER2-positive breast cancer brain metastases [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-16-10.