P08.01 * RESPONSE TO T-DM1 IN HER2-POSITIVE BREAST CANCER BRAIN METASTASES (BM)

Abstract

BACKGROUND: Management ofBM mainly relies on local treatment approaches including whole brain radiotherapy(WBRT), radiosurgery, and neurosurgery depending on number and size of BM. Of note, WBRT is associated with severe late-toxicity. Recently, lapatinib plus capecitabine (LapCap) as primary systemic treatment in oligosymptomatic patients (pts) with multiple Her2-positive BM was shown to achieve considerable response and delay the need for WBRT. T-DM1 (trastuzumab-emtansine) is an antibody-drug conjugate linking trastuzumab (T) to an anti-microtubule agent. T-DM1 provides activity in pts progressing upon T and has lower toxicity as compared to LapCap. Here, we investigated the activity of T-DM1 in newly diagnosed or progressive BM. PATIENTS AND METHODS: Six pts (median age 55 years) with Her2-positive breast cancer and BM were treated with T-DM1. Twoasymptomatic pts receivedT-DM1as first line therapy for brain metastatic disease, while four pts received local therapy before and had documented CNS progression at inclusion. T-DM1 was administered intravenously at a dose of 3.6 mg/kg body weight every three weeks; re-assessment of disease status was performed every three cycles. At baseline and restaging, MRI was performed. CNS response was defined as a reduction of lesion size of ≥50%. RESULTS: Median follow-up was 6 months (m). All pts had received prior T, 3/6 (50%) had already received LapCap, and 2/6 (33.3%) pertuzumab. Currently, 4/6 pts (66.6%) are assessable for CNS response. Two/4 pts (50%) had partial remission, while one patient progressing upon prior local therapy had stable disease. One/6 (16.6%) patient had minor response on MRI but no reduction of pre-existing brain oedema and increasing cortisol doses and was therefore deemed PD. A significant LVEF drop was observed in one heavily pretreated patient. CONCLUSION: This prospective case series again indicates that systemic therapy offers activity in Her2-positive BM. Currently, primary systemic treatment with LapCap remains the standard of care. Still, T-DM1 is well tolerated and offers relevant clinical activity; therefore, the role of T-DM1 in BM should be investigated in larger studies.