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Randomized Controlled Trial
. 2023 Oct;10(5):3174-3183.
doi: 10.1002/ehf2.14466. Epub 2023 Jul 14.

Sacubitril/valsartan for cardioprotection in breast cancer (MAINSTREAM): design and rationale of the randomized trial

Mateusz Tajstra  1 , Maciej Dyrbuś  1 , Tomasz Rutkowski  2 , Krzysztof Składowski  2 , Barbara Sosnowska-Pasiarska  3 , Stanisław Góźdź  4 , Barbara Radecka  5   6 , Marek Staszewski  7 , Aleksandra Majsnerowska  1 , Krzysztof Myrda  1 , Alicja Nowowiejska-Wiewióra  1 , Ilona Skoczylas  1 , Igor Rymkiewicz  8 , Tomasz Niklewski  9 , Jolanta Nowak  1 , Piotr Przybyłowski  9 , Mariusz Gąsior  1 , Michał Jarząb  10
Affiliations
Randomized Controlled Trial

Sacubitril/valsartan for cardioprotection in breast cancer (MAINSTREAM): design and rationale of the randomized trial

Mateusz Tajstra et al. ESC Heart Fail. 2023 Oct.

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).

Keywords: Breast cancer; Cardio-oncology; Cardiotoxicity; Heart failure; Randomized trial; Sacubitril/valsartan.

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Conflict of interest statement

None declared.

Figures

Figure 1
Figure 1
The study design. ECG, electrocardiography; ESC, European Society of Cardiology; LVEF, left ventricular ejection fraction; MRI, magnetic resonanse imaging.
See this image and copyright information in PMC

References

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