Dowsing Benjamin, Dehbi Hakim-Moulay, Chung Robin, Pedra Joanna, Worn Orla, Artico Jessica, Schmid Peter, Roylance Rebecca, Kellman Peter, Moon James C, Crake Tom, Westwood Mark, Ghosh Arjun, Andres Maria Sol, Nazir Muhummad Sohaib, Lyon Alexander R, Chen Daniel, Walker Malcolm, Manisty Charlotte H
Institute of Cardiovascular Science, University College London, London, UK.
Saint Bartholomew's Hospital Barts Heart Centre, London, UK.
BMJ Open. 2025 Feb 5;15(2):e091917. doi: 10.1136/bmjopen-2024-091917.
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for Recovered HER2 Targeted Therapy Related Cardiac Dysfunction (HER-SAFE) aims to evaluate whether HFT can be safely withdrawn in non-high cardiovascular (CV) risk patients with 'recovered' HER2 CTRCD.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.
四分之一的乳腺癌表现为人表皮生长因子-2（HER2）过表达，针对这种情况的靶向治疗可显著提高生存率。然而，高达15%的患者会出现癌症治疗相关的心脏功能障碍（CTRCD）。在必要时中断HER2治疗并启动心力衰竭治疗（HFT）后，超过80%的HER2 CTRCD患者的心脏功能会恢复。HER2治疗完成后，对于“已恢复”的HER2 CTRCD患者是否需要继续进行HFT尚不清楚，而且这可能对患者的生活质量（QoL）产生重大影响。“HER2靶向治疗相关心脏功能障碍恢复后停药安全性随机对照试验（HER-SAFE）”旨在评估对于“已恢复”HER2 CTRCD的非高心血管（CV）风险患者，是否可以安全停用HFT。
这是一项多中心、开放标签的随机对照试验，旨在研究对于癌症治疗完成后“已恢复”HER2 CTRCD的非高CV风险乳腺癌幸存者，停用HFT是否不劣于继续使用HFT。主要终点是指南定义的心脏功能障碍或临床心力衰竭的发生率。次要终点包括心脏血液生物标志物的变化、心血管磁共振（CMR）衍生的应变和组织成像以及心力衰竭症状问卷。该研究将招募90名参与者，他们将在12个月内接受系列临床评估，包括先进的心血管成像（基线、6个月和12个月时进行自动分析的CMR扫描）、心脏生物标志物测量（12个月内6个时间点），以及完整的心力衰竭QoL和药物无用性问卷。这是第一项解决这一重大临床问题的多中心研究。
本研究已获得研究伦理委员会批准（伦敦-伦敦桥，23/LO/0152）。研究结果将在同行评审的科学期刊上发表。
NCT05880160。
