Cardiac safety in a phase II study of trastuzumab emtansine (T-DM1) following anthracycline-based chemotherapy as adjuvant or neoadjuvant therapy for early-stage HER2-positive breast cancer.

532 Background: T-DM1 has demonstrated clinical activity as a single agent in patients (pts) with previously untreated MBC. In a previous phase II randomized trial of T-DM1 vs trastuzumab + docetaxel, T-DM1 had no clinically significant cardiac events, no cases of post-baseline left ventricular ejection fraction (LVEF) ≤40%, and fewer grade ≥3 adverse events (AEs; Hurvitz, ESMO 2011). This phase II study assessed the clinical safety and feasibility of T-DM1 following anthracycline-based chemotherapy in the adjuvant or neoadjuvant setting for early-stage HER2-positive breast cancer. Methods: TDM4874g (NCT01196052) is a phase II single-arm, open-label study of T-DM1 (3.6 mg/kg q3w IV; up to 17 cycles) following completion of doxorubicin/cyclophosphamide (AC; q2w or q3w for 4 cycles), or 5-fluorouracil/epirubicin (100 mg/m2)/cyclophosphamide (FEC; q3w for 3-4 cycles) chemotherapy in pts with early-stage HER2-positive breast cancer. Pre-chemotherapy LVEF by MUGA/ECHO ≥55% was required for enrollment. Co-prima...