ABSTRACT
AIMS: In recent years, survival in patients with breast cancer has increased. Despite the improvement in outcomes of those patients, the risk of treatment-related cardiotoxicity remains high, and its presence has been associated with a higher risk of treatment termination and thus lower therapeutic efficacy. Prior trials demonstrated that a preventive initiation of heart failure drugs, including the renin-angiotensin-aldosterone inhibitors, might reduce the risk of treatment-related cardiotoxicity. However, to date, no study investigated the efficacy of sacubitril/valsartan, a novel antineurohormonal drug shown to be superior to the previous therapies, in the prevention of cardiotoxicity in patients with early-stage breast cancer, which is the aim of the trial. METHODS AND RESULTS: MAINSTREAM is a randomized, placebo-controlled, double-blind, multicentre, clinical trial. After the run-in period, a total of 480 patients with early breast cancer undergoing treatment with anthracyclines and/or anti-human epidermal growth factor receptor 2 drugs will be randomized to the highest tolerated dose of sacubitril/valsartan, being preferably 97/103 mg twice daily or placebo in 1:1 ratio. The patients will be monitored, including routine transthoracic echocardiography (TTE) and laboratory biomarker monitoring, for 24 months. The primary endpoint of the trial will be the occurrence of a decrease in left ventricular ejection fraction by ≥5% in TTE within 24 months. The key secondary endpoints will be the composite endpoint of death from any cause or hospitalization for heart failure, as well as other imaging, laboratory, and clinical outcomes, including the occurrence of the cancer therapy-related cardiac dysfunction resulting in the necessity to initiate treatment. The first patients are expected to be recruited in the coming months, and the estimated completion of the study and publication of the results are expected in December 2027, pending recruitment. CONCLUSIONS: The MAINSTREAM trial will determine the efficacy and safety of treatment with sacubitril/valsartan as a prevention of cardiotoxicity in patients with early breast cancer (ClinicalTrials.gov number: NCT05465031).
ABSTRACT
BACKGROUND: Cardiovascular diseases are the most common factor affecting prognosis in cancer survivors. Cardiooncology (CO) services have been developed to solve this issue. The outcomes regarding patient demographics and clinical findings are limited and the available data include CO services evaluating patients undergoing only chemotherapy as opposed to those also undergoing radiation therapy. AIMS: We aimed to show initial experiences of the CO service implemented in a tertiary oncology center. METHODS: The CO service was designed to include 2 major domains, general CO and electrotherapy consultations. This observational study included patients referred to the CO service with the following data: baseline demographics, cancer type, reasons for referral, cardiac evaluation, and initial clinical outcomes. RESULTS: All patients with cancer referred to our CO service between March 2016 and December 2019 were included in the study. A total of 2762 patients (77% women) at the mean (SD) age of 62 (12) years were referred (63% on an outpatient basis) for general consultations. The most frequent diagnosis was breast cancer (66%). A total of 18% of patients were referred to the CO service due to cardiovascular complications related to cancer treatment. The CO-cardiac implantable electronic device (CIED) team evaluated 652 patients (515 patients with CIEDs who were qualified for radiotherapy, 48 patients with CIEDs who were assessed with magnetic resonance imaging, and 89 patients with CIEDs who underwent cancer surgery). In the total of 5872 radiotherapy sessions, there were 2 harmful interactions; no other complications during magnetic resonance imaging and surgery were recorded. CONCLUSIONS: The COservice established within the cancer center seems to be safe and feasible.
