Sacubitril/Valsartan in PriMAry preventIoN of the Cardiotoxicity of Systematic breaST canceR trEAtMent (MAINSTREAM)

Launched by SILESIAN CENTRE FOR HEART DISEASES · Jul 15, 2022

Keywords

ClinConnect Summary

The MAINSTREAM trial is studying whether a medication called sacubitril/valsartan can help prevent heart problems in women with breast cancer who are receiving specific chemotherapy treatments. Breast cancer treatment can sometimes lead to heart issues, which can make it necessary to stop cancer treatment. This trial will involve 480 women aged 18 and older who have been diagnosed with breast cancer and are planning to use certain chemotherapy drugs. Participants will be randomly assigned to receive either sacubitril/valsartan or a placebo (a pill that looks the same but has no active medication) for 24 months. Throughout the study, participants will undergo various health checks, including heart imaging tests and assessments of their overall health and quality of life.

To be eligible for the trial, women must have a confirmed diagnosis of breast cancer, be able to take oral medications, and have a good general health status. However, those who have had certain prior treatments or have other significant health issues may not be able to participate. This study is important because it could help find ways to protect the heart during cancer treatment, allowing more women to receive the care they need without risking heart problems.

Gender

FEMALE

Eligibility criteria

• Inclusion Criteria:
• • Written informed consent
• • Female gender, aged 18 years and over
• • Patients with histologically confirmed breast cancer and complete assessment of tumor phenotype (Estrogen receptor - ER, Progesterone receptor - PR, Human epidermal growth factor receptor 2 - HER2, Kiel - Ki67)
• • Ability to take oral medication and willingness to adhere to the planned regimen
• • Tumor grade IA-IIIC or oligometastatic grade IV
• • Radical treatment plan including surgery
• • Plan of use of systemic treatment (preoperative, postoperative or combined) with anthracyclines and/or anti-HER2 drugs
• • Eastern Cooperative Oncology Group (ECOG) 0-2 general status
• • LVEF ≥ 50% as assessed by echocardiography
• • Sinus rhythm
• Exclusion Criteria:
• • Prior anthracycline-based chemotherapy and/or thoracic radiotherapy (prior to diagnosis of the cancer being the present cause of therapy)
• • Clinically relevant HF (NYHA II-IV)
• • Myocardial infarction (MI) within the last \< 3 months
• • Symptomatic hypotension or systolic blood pressure (SBP) \< 90 mmHg
• • Significant valvular disease, symptomatic coronary artery disease (CCS\>2), significant atrioventricular (AV) block, symptomatic sinus node dysfunction
• • Expected survival \<12 months
• • Glomerular filtration rate (GFR) \<30 ml/min/1.73 m2 (screening visit)
• • K+\>5.5mmol/L (screening visit)
• • Contraindications to angiotensin converting enzyme inhibitor (ACE-I)/angiotensin II receptor blocker (ARB) or LCZ696 if not listed among criteria
• • Active untreated liver disease
• • Pregnancy
• • Conditions/circumstances that may lead to non-compliance with medical staff recommendations (e.g. active drug/alcohol dependence, poorly controlled mental illness)