Cardiac safety of adjuvant pegylated liposomal doxorubicin with concurrent trastuzumab: a randomized phase II trial.

BACKGROUND: The cardiac safety of trastuzumab concurrent with pegylated liposomal doxorubicin (PLD) in an adjuvant breast cancer treatment regimen is unknown. PATIENTS AND METHODS: Women with resected node-positive or intermediate-risk node-negative HER2 overexpressing breast cancer and baseline left ventricular ejection fraction (LVEF)≥55% were randomized (1:2) to doxorubicin 60 mg/m2 (A)+cyclophosphamide 600 mg/m2 (C) every 21 days (q21d) for four cycles or PLD 35 mg/m2+C q21d+trastuzumab 2 mg/kg weekly (H) for 12 weeks. Both groups then received paclitaxel (Taxol, T) 80 mg/m2 with H for 12 weeks followed by H to complete 1 year. The primary end point was cardiac event rate or inability to administer 1 year of trastuzumab. RESULTS: Of 181 randomized patients, 179 underwent cardiac analysis. The incidence of cardiac toxicity or inability to administer trastuzumab due to cardiotoxicity was 18.6% [n=11; 95% confidence interval (CI) 9.7% to 30.9%] with A+C→T+H and 4.2% (n=5; 95% CI 1.4% to 9.5%) with PLD+C+H→T+H (P=0.0036). All events, except one, were asymptomatic systolic dysfunction or mildly symptomatic heart failure. Mean absolute LVEF reduction at cycle 8 was greater with doxorubicin (5.6% versus 2.1%; P=0.0014). CONCLUSION: PLD+C+H→T+H is feasible and results in lower early cardiotoxicity rates compared with A+C→T+H.