CC Cardiol Croat Cardiologia Croatica Cardiol. Croat. 1848-543X 1848-5448 Croatian Cardiac Society CC_13(11-12)_466 10.15836/ccar2018.466 Extended Abstract Effects of trastuzumab and trastuzumab-emtansine on QTc intervals Učinci primjene trastuzumaba i trastuzumab-emtansina na QTc interval https://orcid.org/0000-0001-8446-6120Lovrić BenčićMartina1*https://orcid.org/0000-0001-8296-699XBradićLada1https://orcid.org/0000-0003-3687-1310LevickiRea2https://orcid.org/0000-0002-3189-1518JugJuraj3BegovacMartahttps://orcid.org/0000-0003-0263-339x3https://orcid.org/0000-0002-0027-9676MihajlovićMarina1 Medicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska Opća županijska bolnica Požega, Požega, Hrvatska Medicinski fakultet Sveučilišta u Zagrebu, Zagreb, Hrvatska University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia Požega County Hospital, Požega, Croatia University of Zagreb School of Medicine, Zagreb, Croatia ADDRESS FOR CORRESPONDENCE: Martina Lovrić Benčić, Klinički bolnički centar Zagreb, Kišpatićeva 12, HR-10000 Zagreb, Croatia. / Phone: +385-91-228-2240 / Email: mlbencic@icloud.com 112018 13 11-12 466 467 2610201805112018 2018 Croatian Cardiac Society KLJUČNE RIJEČI: trastuzumabtrastuzumab s emntansinomQTc intervalHER2+ karcinom dojke KEYWORDS: trastuzumabtrastuzumab-emntansineQTc intervalHER2+ breast cancer

Introduction: Trastuzumab and trastuzumab-emtansine are antibody drugs and antibody-conjugate for human epidermal growth factor receptor 2 (HER2)- positive breast cancer. Their possible side effects can be QT prolongation and reduction of left ventricular ejection fraction (LVEF), as previously documented. (1-3)

Methods and Results: All patients were previously treated with standard regimen: paclitaxel and cisplatinum. After that they received specific antibody drugs. The aim of this study was to test their effect on QTc interval in our patients. A total of 26 patients with preserved LVEF were treated with trastuzumab and before every application, ECG was obtained and analyzed. Later on, 24 patients (aged 57.33 years; 46-69 years) continued the treatment with trastuzumab-emtansine because of metastatic disease. Due to reduction of LVEF two patients could not continue with therapy. The last ECG was obtained 6 months after the last drug application. Statistical analysis was performed using standard t-test. Significant QTc prolongation was noticed after the third application of both drugs, continued during the fourth, fifth and sixth application of both drugs and normalization was noticed after six months without therapy. Results are shown in tables 1, 2 and 3.

Average duration of QTc intervals.
Average duration of QTc intervals (ms)
TRASTUZUMAB TRASTUZUMAB+EMTANSIN
Before th.1 447.4750 448.6250
4 469.8750 470.1250
5 471.0833 474.4583
6 469.6667 471.8750
6 months after administration of the last dose 7 451.4583 454.4167
Statistical significance of QTc prolongation compared to initial values (QTc1).
QTc interval - comparison p-valueTRASTUZUMAB CI (95%)TRASTUZUMAB p-value TRASTUZUMAB+EMTANSINE CI (95%)TRASTUZUMAB+EMTANSINE
QTc1 vs QTc4 0.007907 6.192 – 38.807 0.002223 8.143 – 34.857
QTc1 vs QTc5 0.002470 8.809 – 38.607 0.000605 11.714 – 39.953
QTc1 vs QTc6 0.005007 7.072 – 37.511 0.000757 10.280 – 36.219
Statistical significance of QTc prolongation compared to the control value 6 months after the last drug application (QTc7).
QTc interval - comparison p-valueTRASTUZUMAB CI (95%)TRASTUZUMAB p-valueTRASTUZUMAB+EMTANSINE CI (95%)TRASTUZUMAB+EMTANSINE
QTc7 vs QTc4 0.022461 2.722 – 34.111 0.018883 2.717 – 28.699
QTc7 vs QTc5 0.007911 5.399 – 33.851 0.005280 6.267 – 33.816
QTc7 vs QTc6 0.015374 3.648 – 32.768 0.007633 4.865 – 30.051

Conclusion: Treatment with trastuzumab and also with trastuzumab-emtansine significantly prolonged QTc interval in patients with breast cancer, but the change was reversible after the cessation of treatment.

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