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

Abstract

BACKGROUND: Management of BM 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. Two asymptomatic pts received T-DM1 as 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.