Cardioprotective agents for the primary prevention of trastuzumab-associated cardiotoxicity: a systematic review and Meta-Analysis

Abstract

In recent years, the incidence of breast cancer has been increasing on an annual basis. Human epidermal growth factor receptor-2 (HER2) is overexpressed in 15-25% human breast cancers, which is associated with poor prognosis and a high recurrence rate. Trastuzumab is the first humanized monoclonal antibody against HER2. Trastuzumab-induced cardiac dysfunction is one of the major side effects of trastuzumab therapy in breast cancer patients and the main reason for discontinuation, which significantly limits its safe use. Unfortunately, the mechanism causing this cancer therapy-related cardiac dysfunction (CTRCD) is still not completely understood and the use of preventive interventions remains controversial. Recently, randomized controlled trials (RCTs) have evaluated the effects of early initiation of beta-blockers (BBs), angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) during trastuzumab chemotherapy to prevent associated CTRCD. The present systematic review and meta-analysis of six RCTs included patients who had predominantly non-metastatic, HER2-positive, breast cancer and received trastuzumab as primary or adjuvant therapy. These patients had no apparent cardiac dysfunction or prior treatment with a cardioprotective agent. We evaluated the efficacy of the aforementioned drugs for primary prevention of CTRCD using random-effects models. Any preventive therapy did not reduce the incidence of CTRCD compared with controls (odds ratios (OR) = 0.92, 95% CI 0.54-1.56, p = 0.75). Results were similar for ACEIs/ARBs and β-blockers. Treatment with ACEIs/ARBs resulted in a small, but significant, increase in LVEF in patients compared to the placebo group. Only two studies reported a lower probability of discontinuation of trastuzumab treatment. More sufficiently powered RCTs are needed to determine the efficacy of routine prophylactic therapy.