Evaluation of cardiac safety of lapatinib therapy for c-erbB2 amplified metastatic breast cancer.

Abstract

e11001 Background: Lapatinib (L) is a tyrosine kinase inhibitor (TKI) that has efficacy in breast cancer. This study assessed the cardiac safety of lapatinib in women with cerbB-2 amplified metastatic breast cancer. Methods: In this study, 26 patients who were previously treated with anthracyclines, taxanes and trastuzumab were assigned to receive lapatinib (L) plus capecitabine (C). Cardiac toxicity was assessed with symptoms, transthoracic echocardiography, electrocardiography (ECG), brain natriuretic peptide (BNP), creatine kinase (CK) and CK-MB at baseline and every 9 weeks until progression. Results: A total of 26 patients were treated with L+C for a median follow-up of 18 weeks. The median age was 48 (28-83) years. Among 25 eligible patients, 8 (30,8%) had ECG changes one of which was grade I QT prolongation and 2 (7.7%) had decreased left ventricular ejection fraction (LVEF) below critical level (>15% drop compared to baseline or below normal level). Although there were no clinically observed cardiac symptoms, lapatinib was stopped in one patient who had decreased LVEF. The patient showed recovery of LVEF after three cycles of capecitabine monotherapy. Lapatinib was restarted and L+C therapy was continued until progression. The other patient who also had decreased LVEF, contiuned L+C therapy. LVEF normalized after 3 cycles of L+C combination therapy. Both patients are alive without any cardiac problems. The patient with grade I QT prolongation continued the therapy and after 3 cycles QT distance turned to normal limits. Among eligible 21 patients, 2 had increased BNP, 1 had increased CK and 1 had increased CK-MB level compared to baseline. There were no symptomatic cardiac events which required monitorization and intervention. Statistically, there was no significant relationship between duration of lapatinib administration and LVEF changes, QT distance prolongation, BNP, CK and CK-MB level. Conclusions: Lapatinib is safe and has lower cardiac side effects than other TKIs. Thus cardiotoxicity is not a class effect of TKIs. Despite no clinically serious cardiac side effects of lapatinib were observed in this study, the incidence of cardiac side effects is higher than previously reported lapatinib studies.