Effects of trastuzumab and trastuzumab emtansine on corrected QT interval and left ventricular ejection fraction in patients with metastatic (HER2+) breast cancer.

Background: Trastuzumab and trastuzumab emtansine are specific antibody and antibody-drug conjugates used in the treatment of human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer. The aim of this study was to test their effect on the QTc interval duration and left ventricular ejection fraction (LVEF) in our patients, two parameters used in evaluation of cardiotoxicity. From May 2015 to October 2017, 26 patients with preserved LVEF were included in the study. All of them were previously treated with standard paclitaxel and cisplatin-based chemotherapy regimens. Electrocardiogram (ECG) was recorded just before each trastuzumab dose application and six months after the last dose. Echocardiography with LVEF measurement was performed several days before the application of the initial dose, and six months after the last cycle. Later, 24 patients with metastatic disease received additional treatment with trastuzumab emtansine after six months and the same ECG and echocardiography protocol was performed again. Due to reduction in LVEF, two patients were discontinued from additional treatment.

Results: A statistically significant QTc prolongation was found after each drug dose application, with an increase in mean QTc duration with every successive application, reaching the peak QTc values just before the fifth cycle of treatment. The QTc interval returned to its initial value six months after the last cycle (p < 0.001). These results were similar for both drugs. Mean LVEF before both treatment protocols was significantly higher compared to LVEF value after the treatment. LVEF before trastuzumab emtansine treatment was non-significantly higher than LVEF after trastuzumab treatment.

Conclusion: Trastuzumab and trastuzumab emtansine cardiotoxicity manifested as a significant and progressive QTc prolongation after successive drug applications, reaching the peak value just before the fifth cycle of both drugs. Both medications also caused statistically significant but asymptomatic LVEF reduction. Complete reversibility of cardiotoxic effects of both drugs was confirmed by QTc interval and LVEF normalisation after the treatment discontinuation.