M15. The potential benefits of renin-angiotensin-aldosterone and beta-adrenergic inhibitions for lowering trastuzumab-associated cardiotoxicity risks among breast cancer patients: meta-analysis of randomized controlled trials

Trastuzumab is one of the principal treatments for HER2-positive breast cancer patients and related to high cardiotoxicity risk. This study aims to compare the efficacies among Renin-Angiotensin-Aldosterone inhibitors (RAASi) and beta-blockers (BB) to lower trastuzumab-associated cardiotoxicity risks.

Comprehensive literature searching was conducted through online databases then followed the PRISMA guideline. Studies included were all randomized controlled trials (RCTs) that compared the changes of left ventricular ejection fraction (LVEF) and brain natriuretic peptides (BNP) among RAASi, BB, and placebo (PCB) in HER2-positive breast cancer patients who received trastuzumab. Bias risk was accessed by using the Cochrane Risk-of-bias (RoB 2) instrument. Analysis was performed to provide pooled risk ratio (RR) and standard mean difference (SMD) with 95% confidence interval (CI) using fixed-effect heterogeneity test. The RAASi group shows significant LVEF improvement compared with PCB (SMD=0.63, 95%CI 0.27 to 0.99, p = 0.0006, I²=0%), while the BB group also shows LVEF improvement compared with PCB although not statistically significant (SMD=0.04, 95%CI -0.32 to 0.39, p = 0.84, I²=0%). Both RAASi (SMD=0.18, 95%CI 0.00 to 0.37, p = 0.05, I²=0%) and BB (SMD=0.23, 95%CI 0.05 to 0.42, p = 0.01, I²=0%) groups have significant BNP improvement. Patients received RAASi have significant reduction of 2-year cardiac risk development (RR = 0.42, 95%CI 0.27-0.67, p = 0.0002, I²=42%) and non-significance LVEF <50% reduction risk (RR = 0.49, 95%CI 0.23-1.08, p = 0.08, I²=50%).

Both RAASi and BB show potential benefits in lowering the trastuzumab-associated cardiotoxicity risks. However, further studies are needed to establish the efficacies.