Journal Article

Long-term follow-up assessment of cardiac safety in SAFE-HEaRt, a clinical trial evaluating the use of HER2-targeted therapies in patients with breast cancer and compromised heart function

Smith, Karen L, Warren, Robert, Isaacs Claudine, Geng Xue, Lynce Filipa, Herbolsheimer Pia, Barac Ana, Srichai, Monvadi B, Swain, Sandra M, Nunes, Raquel, Dang Chau, Khoury Katia, Hofmeyer, Mark, Gallagher, Christopher, Yu, Anthony F, Pohlmann, Paula R, Tan, Ming, Asch Federico

2021

Overview

PurposeHER2-targeted therapies are associated with cardiotoxicity which is usually asymptomatic and reversible. We report the updated cardiac safety assessment of patients with compromised heart function receiving HER2-targeted therapy for breast cancer, enrolled in the SAFE-HEaRt trial, at a median follow-up of 3.5 years.MethodsThirty patients with stage I-IV HER2-positive breast cancer receiving trastuzumab with or without pertuzumab, or ado-trastuzumab emtansine (T-DM1), with asymptomatic LVEF (left ventricular ejection fraction) 40–49%, were started on cardioprotective medications, with the primary endpoint being completion of HER2-targeted therapy without cardiac events (CE) or protocol-defined asymptomatic worsening of LVEF. IRB-approved follow-up assessment included 23 patients.ResultsMedian follow-up as of June 2020 is 42 months. The study met its primary endpoint with 27 patients (90%) completing their HER2-targeted therapies without cardiac issues. Of the 23 evaluable patients at long-term f/u, 14 had early stage breast cancer, and 9 had metastatic disease, 8 of whom remained on HER2-targeted therapies. One patient developed symptomatic heart failure with no change in LVEF. There were no cardiac deaths. The mean LVEF improved to 52.1% from 44.9% at study baseline, including patients who remained on HER2-targeted therapy, and those who received prior anthracyclines.ConclusionsLong-term follow-up of the SAFE-HEaRt study continues to provide safety data of HER2-targeted therapy use in patients with compromised heart function. The late development of cardiac dysfunction is uncommon and continued multi-disciplinary oncologic and cardiac care of patients is vital for improved patient outcomes.

• Publisher: Springer Nature B.V
• Subject: Anthracycline / Asymptomatic / Breast cancer / Cancer research / Cardiotoxicity / Congestive heart failure / ErbB-2 protein / Heart / Immunotherapy / Metastases / Monoclonal antibodies / Patients / Safety / Targeted cancer therapy / Trastuzumab / Ventricle