Prospective evaluation of the cardiac safety of HER2-targeted therapies in patients with HER2-positive breast cancer and compromised heart function: the SAFE-HEaRt study

Abstract

Purpose HER2-targeted therapies have substantially improved the outcome of patients with breast cancer, however, they can be associated with cardiac toxicity. Guidelines recommend holding HER2-targeted therapies until resolution of cardiac dysfunction. SAFE-HEaRt is the first trial that prospectively tests whether these therapies can be safely administered without interruptions in patients with cardiac dysfunction. Methods Patients with stage I–IV HER2-positive breast cancer candidates for trastuzumab, pertuzumab or ado-trastuzumab emtansine (TDM-1), with left ventricular ejection fraction (LVEF) 40–49% and no symptoms of heart failure (HF) were enrolled. All patients underwent cardiology visits, serial echocardiograms and received beta blockers and ACE inhibitors unless contraindicated. The primary endpoint was completion of the planned HER2-targeted therapies without developing either a cardiac event (CE) defined as HF, myocardial infarction, arrhythmia or cardiac death or significant asymptomatic worsening of LVEF. The study was considered successful if planned oncology therapy completion rate was at least 30%. Results Of 31 enrolled patients, 30 were evaluable. Fifteen patients were treated with trastuzumab, 14 with trastuzumab and pertuzumab, and 2 with TDM-1. Mean LVEF was 45% at baseline and 46% at the end of treatment. Twenty-seven patients (90%) completed the planned HER2-targeted therapies. Two patients experienced a CE and 1 had an asymptomatic worsening of LVEF to ≤ 35%. Conclusion This study provides safety data of HER2-targeted therapies in patients with breast cancer and reduced LVEF while receiving cardioprotective medications and close cardiac monitoring. Our results demonstrate the importance of collaboration between cardiology and oncology providers to allow for delivery of optimal oncologic care to this unique population. Electronic supplementary material The online version of this article (10.1007/s10549-019-05191-2) contains supplementary material, which is available to authorized users.

Clinical impact of interruption in adjuvant Trastuzumab therapy in patients with operable HER-2 positive breast cancer

“…Trastuzumab can subsequently be restarted with resolution of cardiac dysfunction. However, since completion of this study, two = single arm prospective trials, SCHOLAR [ 39 ] and SAFE-HEaRt [ 22 ], have investigated the continuation HER2-targeted therapy while concomitantly starting cardioprotective therapy in patients who develop mildly reduced LVEF. Although larger and randomized trials are needed, both of these studies demonstrate safety data with lack of further deterioration in cardiac function in approximately 90% of cases.…”

“…Older age (> 50 years) and pre-existing cardiovascular (CV) diseases, such as uncontrolled hypertension and congestive heart failure, have been implicated in increasing the risk of TIC [ 10 , 15 – 19 ]. The incidence of TIC is also higher in patients receiving concomitant or sequential anthracycline (up to 27%) compared to non-anthracycline regimens [ 4 , 20 – 22 ]. Several randomized trials have evaluated shorter duration of adjuvant trastuzumab with a goal of minimizing cardiotoxicity while maintaining efficacy of systemic therapy [ 23 – 26 ].…”

Adjuvant Trastuzumab Therapy: Can We Balance Efficacy and Safety?

“…The SAFE‐HEaRT trial is a similar study evaluating the safety of continuing HER2 targeted therapies with concomitant with ACE‐I/beta‐blocker treatment in patients with mildly decreased left ventricular function . In this study, 3 of 30 evaluated patients experienced cardiac events (2 experienced symptomatic heart failure, 1 experienced LVEF <35%).…”

Opções Contemporâneas de Rastreio da Cardiotoxicidade Relacionada a Tratamentos Oncológicos

“…Estudos publicados e outros em andamento são destinados à esfera da prevenção baseada no uso de medicações que, porventura, reduziriam o dano cardíaco (inibidores da enzima conversora de angiotensina, betabloqueadores) 42 . Outras linhas de pesquisa exploram o melhor manejo de pacientes com doença miocárdica preexistente 43 .…”