355PSafety and efficacy of T-DM1 in 128 patients with advanced HER2+ breast cancer: The Royal Marsden experience

Abstract Background Ado-trastuzumab emtansine (T-DM1) is standard of care for patients with advanced HER2+ breast cancer who relapse within 6 months of adjuvant trastuzumab or progress on anti-HER2 therapy. Hepatotoxicity on T-DM1 requires careful monitoring especially on long-term treatment. We evaluated its safety and efficacy in our real-world population, with particular attention to liver toxicity. Methods We identified patients on T-DM1 from 01/01/2014 to 12/03/2018 from our electronic records. Patients’ and tumour characteristics were recorded, along with safety and efficacy outcomes. Chi-squared/Fishers exact test and Kaplan-Meier statistical methods were utilised. Results 128 patients treated with T-DM1 were included in the analysis with a median age of 55 years (26-85). 115 (89.8%) had ECOG PS 0-1 and 95 (74.2%) were postmenopausal. 27 (21.1%) had de novo metastatic, 74 (57.8%) ER-positive disease. Metastatic spread involved bones in 82 patients (64.1%), liver in 71 (55.5%), lung in 62 (48.4%), nodes in 78 (60.9%), chest wall in 26 (20.3%) and central nervous system in 49 (38.3%). All patients had received prior trastuzumab and 39 (30.5%) pertuzumab. Neutropenia occurred in 29 patients (22.7% - G3-4 in 1 [3.5%]), anemia in 51 (39.2% - G3-4 in 8 [15.7%] and thrombocytopenia in 56 (43.8% - G3-4 in 6 [12.8%]). 88 patients (68.8%) had deranged liver function (G3-4 in 25 [28.4%]), 5 (3.9%) spider naevi and 12 (9.4%) bleeding. 7 patients (5.5%) experienced diarrhoea, 33 (25.8%) nausea, 82 (64.1%) fatigue, 10 (7.8%) skin rash. Cardiotoxicity occurred in 5 patients (3.9%), lung toxicity in 1 (0.8%). 46 (35.9%) required dose reductions, mostly due to neuropathy (30.4%), fatigue (23.9%), thrombocytopenia (17.4%), liver toxicity (17.4%). T-DM1 was stopped due to toxicity in 14 patients (12.6%). Responses were seen in 77 patients (64.1%). Median PFS was 7 months (95% CI 5-8) and OS 15 months (95% CI 12-17). No significant differences were seen based on prior pertuzumab use. Conclusions The safety of T-DM1 in this population is overall similar to those reported in literature, although we observed slightly higher rates of thrombocytopenia and deranged liver function. Responses were higher but more short-lived. Legal entity responsible for the study The Royal Marsden NHS Foundation Trust. Funding Has not received any funding. Disclosure N.M.L. Battisti: Travel / Accommodation / Expenses: Genomic Health; Speaker Bureau / Expert testimony: Pfizer. A. Ring: Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy: Lilly. All other authors have declared no conflicts of interest.