Breast cancer brain metastases responding to primary systemic therapy with T-DM1

Abstract

Brain metastases are frequent in HER2-positive breast cancer and are associated with poor prognosis. Severe neurological symptoms such as neurocognitive decline, aphasia, paresis, seizures and impaired quality of life are common. The standard therapy options for brain metastases comprise local approaches such as radiotherapy, radiosurgery and neurosurgery. Novel treatments are urgently needed to improve patients’ outcomes. Recently, trastuzumab-emtansine (T-DM1), a novel antibody-cytotoxin conjugate has shown favourable activity and been approved for therapy of metastatic HER2-positive breast cancer. However, so far no data are available on brain penetration and intracerebral activity of T-DM1 [1]. Here, we report on a patient with multiple and locally untreated HER2-positive breast cancer brain metastases responding to systemic monotherapy with T-DM1. This patient was offered T-DM1 (3.6 mg/kg body weight every 3 weeks) as palliative second-line treatment in the setting of recurrent liver and newly diagnosed bone and lung lesions after prior first line therapy with docetaxel (100 mg/m) plus trastuzumab (8 mg/kg body weight loading dose, followed by 6 mg/kg) every 3 weeks. Before the first dose of T-DM1 a brain MRI-scan was performed, which revealed a total number of 20 contrast-enhancing brain metastases throughout the brain (12 supratentorial, 8 infratentorial). Two larger lesions were found in the left post-central region with a maximal diameter of 1.6 cm (index lesion M1; Fig. 1a, contrast-enhanced T1-weighted MRI) and in the right occipital region with a maximal diameter of 8 mm (index lesion M2; Fig. 1e, contrast-enhanced T1-weighted MRI), while all other lesions were only 1–2 millimetres in diameter. Fluid attenuated inversion recovery (FLAIR) imaging showed slight peritumoural brain oedema surrounding the index lesion M1 (Fig. 1c). The patient did not suffer from any neurological symptoms; especially no signs of increased cranial pressure or focal neurological deficits were present. Prognostic assessment was performed according to the diagnosis specific graded prognostic assessment (ds-GPA) based upon Karnofsky Performance Score (KPS), breast cancer subtype, and age, whereupon the patient belonged to the most favourable class [2]. In this situation, potential treatment options were extensively discussed in an interdisciplinary tumour conference of breast cancer and brain tumour specialists. As our patient had no neurological symptoms and presented with KPS 100 %, there was no clear indication for immediate initiation of WBRT. We initiated T-DM1 therapy, as T-DM1 was superior to lapatinib plus capecitabine for the control of systemic disease in the prospective randomized phase III EMILIA study [1]. Intense clinical and radiological followup of brain lesions was planned. T-DM1 was well tolerated. Importantly, neither neurological symptoms nor a deterioration of her general health status was observed. A computed tomography restaging conducted after 4 T-DM1 administrations revealed a complete remission of lung metastases and partial remission of liver lesions. The brainMRI also indicated considerable activity of T-DM1: both index lesions showed a significant decrease in size (M1: from 1.6 cm to 0.8 cm, Fig. 1b; M2: from 8 mm to 5 mm, Fig. 1f) as compared to the baseline scan; perifocal oedema of the index lesion M1 had decreased as well (Fig. 1d). No new lesions were evident and all other minute lesions appeared stable in size, but were too small for formal comparative measurements. R. Bartsch A. S. Berghoff M. Preusser (&) Medical University of Vienna, Vienna, Austria e-mail: matthias.preusser@meduniwien.ac.at