Safety and efficacy of T-DM1 in HER2 positive metastatic breast cancer patients: a real word experience.

Background: T-DM1 is an antibody–drug conjugate that combines the antitumor effects of trastuzumab with a cytotoxic antimicrotubule agent that is only released in HER-positive tumor cells. It has been approved for the treatment of patients with HER2 positive metastatic breast cancer (MBC) pre-treated with trastuzumab + taxanes or progressing while on adjuvant trastuzumab, after the pivotal phase III trial EMILIA. The aim of this study is to audit the real life experience with T-DM1 at the University Hospital of Modena. Material and methods: All patients treated with T-DM1 in our Institution between May 2014 – February 2016 were retroprospectively collected. All patients registered at the time of analysis were evaluated for safety and efficacy. Treatment toxicities were graded according to CTCAE version 4.0. Efficacy was assessed as per clinical practice. Results: Twenty-two patients have been treated with T-DM1. The median age was 58 years (range 38-77), 50% of them with ECOG 1-2. With regards to tumor characteristics, 72% were hormonal receptor positive BC and 82% of patients had visceral involvement at the beginning of T-DM1. All patients received previous trastuzumab and taxane, 50% received anthracycline-based therapy too. 27% of patients were pre-treated with at least three prior chemotherapy lines for MBC. Pertuzumab was previously administered to one patient, lapatinib to 8 patients. The median number of T-DM1 cycles was 9 (range 1-30), with 50% of patients receiving 5 or more courses. All patients were assessed for efficacy: 36% obtained PR and 18% SD as the best response. The clinical benefit rate (CR+PR+SD>6months) was 45%. The median PFS was 9.0 months (CI 2.8–20.8). Six patients (27%) out of 22 died. Mild grade transaminitis was the most common side effect observed in 50% of patients, followed by fatigue in 41% of patients, thrombocytopenia in 35% and diarrhea in 28%. No grade 3 adverse events were observed, although two hypersensitivity reactions were reported. Conclusions: T-DM1 administered outside the context of a clinical trial is safe, well tolerated, and with reproducible efficacy, consistent with those published in the EMILIA and TH3RESA studies.