Considering the favorable overall safety profile of trastuzumab emtansine (T-DM1), the low expected rate of cardiotoxicity, and the synergistic effect of anthracyclines with Human Epidermal Growth Factor Receptor 2 (HER2)-targeting agents, it is hypothesized that T-DM1 may be safely combined with non-pegylated liposomal doxorubicin (NPLD). In the THELMA trial, the effect of adding NPLD to T-DM1 was evaluated with the aim of enhancing T-DM1 efficacy using an extensive cardiological assessment in trastuzumab- and taxane-pretreated patients with HER2-positive metastatic breast cancer. Despite an unlikely drug synergism, this combination was generally well tolerated without clinically relevant worsening of cardiac function. No relationship was identified between early predictors of heart failure and left ventricular ejection fraction changes. Thus, the combination of T-DM1 plus NPLD is safe, but this regimen does not seem to improve T-DM1 antitumor activity in this setting.
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