3rd Department of Cardiology, School of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland.
Department of Radiation and Clinical Oncology, Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland.
ESC Heart Fail. 2023 Oct;10(5):3174-3183. doi: 10.1002/ehf2.14466. Epub 2023 Jul 14.
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.
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.
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).
近年来，乳腺癌患者的生存率有所提高。尽管这些患者的治疗结果得到了改善，但治疗相关的心脏毒性风险仍然很高，并且已经发现这种风险与更高的治疗终止风险相关，从而导致治疗效果降低。先前的试验表明，预防性开始使用心力衰竭药物，包括肾素-血管紧张素-醛固酮抑制剂，可能会降低治疗相关心脏毒性的风险。然而，迄今为止，尚无研究调查新型神经激素药物沙库巴曲缬沙坦在预防早期乳腺癌患者心脏毒性方面的疗效，这是该试验的目的。
MAINSTREAM 是一项随机、安慰剂对照、双盲、多中心临床试验。在导入期后，将总共 480 例接受蒽环类药物和/或抗人表皮生长因子受体 2 药物治疗的早期乳腺癌患者随机分为沙库巴曲缬沙坦最高耐受剂量组，优选每日两次 97/103mg 或 1:1 比例的安慰剂。患者将接受 24 个月的监测，包括常规经胸超声心动图（TTE）和实验室生物标志物监测。试验的主要终点是 24 个月内 TTE 中左心室射血分数下降≥5%。关键次要终点将是全因死亡或心力衰竭住院的复合终点，以及其他影像学、实验室和临床结局，包括导致需要开始治疗的癌症治疗相关心脏功能障碍的发生。预计在未来几个月内开始招募第一批患者，预计在 2027 年 12 月完成研究并公布结果，具体取决于招募情况。
MAINSTREAM 试验将确定沙库巴曲缬沙坦治疗早期乳腺癌患者心脏毒性的疗效和安全性（ClinicalTrials.gov 编号：NCT05465031）。
