Safety of Withdrawal of Pharmacological Treatment for Recovered HER2 Targeted Therapy Related Cardiac Dysfunction (HER-SAFE)
Cardiotoxicity, HER2-positive Breast Cancer, Heart Failure
About this trial
This is an interventional treatment trial for Cardiotoxicity focused on measuring Cardiotoxicity, HER2-positive Breast Cancer, Heart Failure, Cancer, Therapy-Related
Eligibility Criteria
Inclusion Criteria: Adult participants (>18 years) A prior diagnosis of human epidermal growth factor receptor 2 (HER2)- targeted therapy related cardiac dysfunction, who currently receive standard heart failure/cardioprotective medications (any combination of angiotensin-converting enzyme [ACE] inhibitors, angiotensin receptor blockers [ARBs] and/or beta-blockers). Cardiac function has 'recovered'. 'Recovery' is defined as absence of heart failure symptoms with left ventricular ejection fraction (LVEF) improved to 50% or greater and N-terminal pro B-type natriuretic peptide (NTproBNP) <125ng/L, for greater than 6 months. Exclusion Criteria: Advanced/ metastatic HER2 positive breast cancer requiring ongoing HER2 therapies or with life expectancy <12months. Patients classed as high/very high cardiovascular risk according to the International Cardio-Oncology Society (ICOS) risk stratification Patients with LVEF <50% prior to HER2-therapy initiation or on completion of anthracycline treatment Patients with ongoing indications for the cardioprotective medication - ACE inhibitors, ARBs and/or beta-blockers Patients with absolute contraindications to cardiovascular magnetic resonance scans (CMR).
Sites / Locations
- St Bartholemew's Hospital
- University College London Hospital
Arms of the Study
Arm 1
Arm 2
Experimental
No Intervention
Treatment Withdrawal
Treatment Continuation
Participants will undergo phased withdrawal of heart failure/ cardioprotective treatments according to a pre-specified algorithm based on the 'Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy' (TRED-HF) study protocol (Halliday et al 2019). Medications will be down titrated in a phased process every 2 weeks over 16 weeks maximum. Drug doses will be reduced by 50% every 2 weeks, until the patient is taking 25% or less of the maximum recommended dose at which point they will be stopped. Monitoring with fortnightly virtual consultations will confirm dose reduction and provide support. Participants will undergo clinical assessment at 6, 14 and 24 weeks and 6, 9 and 12 months with weight, blood pressure, and biomarker measurement. At baseline, 6- and 12-month visits detailed cardiovascular phenotyping using cardiovascular magnetic resonance scans and symptom and disutility questionnaires will be undertaken.
Participants will continue their current heart failure/ cardioprotective treatments. Participants will undergo clinical assessment at 6, 14 and 24 weeks and 6, 9 and 12 months with weight, blood pressure, and biomarker measurement. At baseline, 6- and 12-month visits detailed cardiovascular phenotyping using cardiovascular magnetic resonance scans and symptom and disutility questionnaires will be undertaken.