Central nervous system (CNS) disease during trastuzumab emtansine (T-DM1) for HER2 positive advanced breast cancer (ABC): A single institution experience

Abstract

Background: T-DM1 is an antibody-drug conjugate that does not cross an intact blood-brain barrier. In the EMILIA trial of T-DM1 versus capecitabine/lapatinib for HER2 positive ABC, all patients had baseline brain imaging. Of the 45 patients (9.1%) with baseline CNS disease, 10 (22%) developed CNS progression on T-DM1. A further 9/450 of patients (2%) developed new CNS disease during T-DM1. We assess the frequency of CNS progression in clinical practice, without routine baseline imaging. Methods: A retrospective study of all patients treated with T-DM1 at the Royal Marsden Hospital from 2011-2016. Data collected included baseline characteristics, previous treatment for ABC, sites of metastatic disease, duration of treatment with T-DM1, sites of progression and treatment of CNS progression. Results: Fifty-five patients were identified who had received a median of 2 prior lines of treatment for ABC (range 0-5). Patients received a median of 12 cycles of T-DM1 (range 1-34) and 6 remain on treatment at the time of analysis. Before commencing T-DM1, 16/55 (29%) had known brain disease (treated with whole brain (9/16) stereotactic radiotherapy (6) or both (1)). CNS was the first site of progression in 56% (9/16) patients with baseline CNS disease, with a median time to CNS progression 9.9 months (95% CI 3.9-12.2). In patients without known baseline CNS disease, 17.9% (7/ 39) developed new symptomatic CNS disease (parenchymal in 5, leptomeningeal in 2) during T-DM1 after a median of 7.5 months (95%CI 3.8-9.6). CNS progression was isolated with control of extracranial disease in 4/7 patients. Median time to extracranial progression in all patients was 11.5 months (95% CI 9.1-17.7) and median OS in all patients was 17.8 months (95% CI 14.2-22). In patients with known baseline CNS disease, median OS was 15.3 months, compared to 12.4 months in those who developed CNS disease during T-DM1 and 21.9 months in those without CNS disease. Conclusions: In our study, CNS progression on T-DM1 was more common than previously reported and survival for patients who developed CNS disease was shorter than expected. If confirmed by other studies, our results suggest that surveillance CNS imaging may be required for patients on T-DM1 therapy.