title: Activity of T-DM1 in Her2-positive breast cancer brain metastases.
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.
authors: Comprehensive Cancer Centre Vienna, Medical University of Vienna, Vienna, Austria.|Department of Medicine I, Clinical Division of Oncology, Comprehensive Cancer Center Vienna, Central Nervous System Unit (CCC-CNS), Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
authors: Rupert
authors: R
authors: Bartsch
authors: Comprehensive Cancer Centre Vienna, Medical University of Vienna, Vienna, Austria.|Department of Medicine I, Clinical Division of Oncology, Comprehensive Cancer Center Vienna, Central Nervous System Unit (CCC-CNS), Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
authors: Anna S
authors: AS
authors: Berghoff
authors: Department of Medicine, St. Joseph Hospital, Vienna, Vienna, Austria.
authors: Ursula
authors: U
authors: Vogl
authors: Comprehensive Cancer Centre Vienna, Medical University of Vienna, Vienna, Austria.|Department of Pathology, Medical University of Vienna, Vienna, Austria.
authors: Margaretha
authors: M
authors: Rudas
authors: Comprehensive Cancer Centre Vienna, Medical University of Vienna, Vienna, Austria.|Department of Medicine I, Clinical Division of Oncology, Comprehensive Cancer Center Vienna, Central Nervous System Unit (CCC-CNS), Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
authors: Elisabeth
authors: E
authors: Bergen
authors: Comprehensive Cancer Centre Vienna, Medical University of Vienna, Vienna, Austria.|Department of Surgery, Medical University of Vienna, Vienna, Austria.
authors: Peter
authors: P
authors: Dubsky
authors: Comprehensive Cancer Centre Vienna, Medical University of Vienna, Vienna, Austria.|Department of Radiotherapy, Medical University of Vienna, Vienna, Austria.
authors: Karin
authors: K
authors: Dieckmann
authors: Comprehensive Cancer Centre Vienna, Medical University of Vienna, Vienna, Austria.|Biomedical Imaging and Image-guided Therapy, Division of Molecular and Gender Imaging, Medical University of Vienna, Vienna, Austria.
authors: Katja
authors: K
authors: Pinker
authors: Comprehensive Cancer Centre Vienna, Medical University of Vienna, Vienna, Austria.|Department of Pathology, Medical University of Vienna, Vienna, Austria.
authors: Zsuzsanna
authors: Z
authors: Bago-Horvath
authors: Department of Gynaecology, Hanusch Hospital, Vienna, Austria.
authors: Arik
authors: A
authors: Galid
authors: Department of Medicine, St. Joseph Hospital, Vienna, Vienna, Austria.
authors: Leopold
authors: L
authors: Oehler
authors: Comprehensive Cancer Centre Vienna, Medical University of Vienna, Vienna, Austria.|Department of Medicine I, Clinical Division of Oncology, Comprehensive Cancer Center Vienna, Central Nervous System Unit (CCC-CNS), Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
authors: Christoph C
authors: CC
authors: Zielinski
authors: Comprehensive Cancer Centre Vienna, Medical University of Vienna, Vienna, Austria.|Department of Surgery, Medical University of Vienna, Vienna, Austria.
authors: Michael
authors: M
authors: Gnant
authors: Comprehensive Cancer Centre Vienna, Medical University of Vienna, Vienna, Austria.|Department of Medicine I, Clinical Division of Oncology, Comprehensive Cancer Center Vienna, Central Nervous System Unit (CCC-CNS), Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
authors: Guenther G
authors: GG
authors: Steger
authors: Comprehensive Cancer Centre Vienna, Medical University of Vienna, Vienna, Austria. matthias.preusser@meduniwien.ac.at.|Department of Medicine I, Clinical Division of Oncology, Comprehensive Cancer Center Vienna, Central Nervous System Unit (CCC-CNS), Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria. matthias.preusser@meduniwien.ac.at.
authors: Matthias
authors: M
authors: Preusser
mesh_terms: D000080044:Ado-Trastuzumab Emtansine; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000556:secondary*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008453:Maytansine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics; D012189:Retrospective Studies; D000068878:Trastuzumab
chemical_list: D000080044:Ado-Trastuzumab Emtansine; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D008453:Maytansine; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: Brain metastases; Breast cancer; Her2 positive; Systemic therapy; T-DM1