# HER-SAFE study design: an open-label, randomised controlled trial to investigate the safety of withdrawal of pharmacological treatment for recovered HER2-targeted therapy-related cardiac dysfunction

## TL;DR

This study investigates whether heart failure therapy can be safely stopped in breast cancer patients who have recovered from heart issues caused by HER2-targeted therapy.

## Contribution

The HER-SAFE trial is the first multicentre study to evaluate the safety of withdrawing heart failure therapy in recovered HER2-related cardiac dysfunction patients.

## Key findings

- HER-SAFE will assess if discontinuing heart failure therapy is non-inferior to continuing it in patients with recovered HER2-related cardiac dysfunction.
- The study will use advanced cardiovascular imaging and biomarkers to monitor cardiac health over 12 months.
- Results will inform whether ongoing heart failure therapy is necessary for these patients, potentially improving their quality of life.

## Abstract

A quarter of breast cancers show human epidermal growth factor-2 (HER2) overexpression, where targeted therapy dramatically improves survival. However, cancer therapy-related cardiac dysfunction (CTRCD) occurs in up to 15% of patients. With the interruption of HER2 therapy, if necessary, and the initiation of heart failure therapy (HFT), HER2 CTRCD recovers in over 80% of cases. The need to continue HFT in ‘recovered’ HER2 CTRCD following completion of HER2 therapy is unclear and there are potential significant impacts on patient’s quality of life (QoL). The Randomised Controlled Trial for the Safety of Withdrawal of Pharmacological Treatment for Recovered HER2 Targeted Therapy Related Cardiac Dysfunction (HER-SAFE) aims to evaluate whether HFT can be safely withdrawn in non-high cardiovascular (CV) risk patients with ‘recovered’ HER2 CTRCD.

This is a multicentre, open-label randomised controlled trial investigating whether withdrawal of HFT is non-inferior to continuation in non-high CV risk, breast cancer survivors with recovered HER2 CTRCD after cancer treatment completion. The primary endpoint is the incidence of guideline-defined cardiac dysfunction or clinical heart failure. Secondary endpoints include changes in cardiac blood biomarkers, cardiovascular magnetic resonance (CMR)-derived strain and tissue mapping and heart failure symptom questionnaires. The study will recruit 90 participants who will undergo serial clinical assessment over 12 months with advanced cardiovascular imaging (CMR scans with automated analysis at baseline, 6 and 12 months), cardiac biomarker measurement (six time points over 12 months), plus complete heart failure QoL and medication disutility questionnaires. This is the first multicentre study to address this significant clinical issue.

This study was approved by the research ethics committee (London—London Bridge, 23/LO/0152). The results will be disseminated in peer-reviewed scientific journals.

NCT05880160.