Key result
Prophylactic treatment with oral heart failure therapies did not significantly reduce the risk of HER2-directed antibody-induced cardiotoxicity compared to control (RR 0.90).
Why the study?
Cardiotoxicity occurs in approximately 10% of patients receiving HER2-directed monoclonal antibodies, and while prevention strategies are increasingly published, they are seldom used in clinical practice.
Do prophylactic oral heart failure therapies (ACE-inhibitors, ARBs, or beta-blockers) prevent cardiotoxicity in women with HER2-positive breast cancer receiving trastuzumab?
Systematic Review (n=952)
Do prophylactic oral heart failure therapies (ACE-inhibitors, ARBs, or beta-blockers) prevent cardiotoxicity in women with HER2-positive breast cancer receiving trastuzumab?
Prophylactic use of ACE inhibitors, ARBs, or beta-blockers in breast cancer patients receiving trastuzumab does not significantly reduce LVEF-defined cardiotoxicity but does significantly reduce the rate of HER2 therapy interruptions.
Monoclonal antibodies including trastuzumab, pertuzumab, and antibody-drug conjugates, form the backbone of HER2-positive breast cancer therapy. Unfortunately, an important adverse effect of these agents is cardiotoxicity, occurring in approximately 10% of patients. There is increasing published data regarding prevention strategies for cardiotoxicity, though seldom used in clinical practice. We performed a systematic review and meta-analysis of randomized-controlled trials to evaluate pharmacotherapy for the prevention of monoclonal HER2-directed antibody-induced cardiotoxicity in patients with breast cancer. Online databases were queried from their inception until October 2021. Effects were determined by calculating risk ratios (RRs) and 95% confidence intervals (CI) or mean differences (MD) using random-effects models. We identified five eligible trials. In the three trials (n = 952) reporting data on the primary outcome of cardiotoxicity, there was no clear effect for patients assigned active treatment compared to control (RR = 0.90, 95% CI 0.63 to 1.29, p = 0.57). Effects were similar for ACE-I/ARB and beta-blockers (p homogeneity = 0.50). Active treatment reduced the risk of HER2 therapy interruptions (RR = 0.57, 95% CI 0.43 to 0.77, p < 0.001) with similar findings for ACE-I/ARB and beta-blockers (p homogeneity = 0.97). Prophylactic treatment with ACE-I/ARB or beta-blocker therapy may be of value for cardio-protection in patients with breast cancer prescribed monoclonal antibodies. Further, adequately powered randomized trials are required to define the role of routine prophylactic treatment in this patient group.
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Brown et al. (2021) conducted a systematic review in HER2-positive breast cancer (n=952). Oral heart failure therapies (ACE-inhibitors, ARBs, or beta-blockers) vs. Placebo or no treatment was evaluated on Cardiotoxicity (absolute reduction in LVEF of ≥10% or a reduction in LVEF to <50% from any baseline value) (RR 0.90, 95% CI 0.63 to 1.29, p=0.57). Prophylactic treatment with oral heart failure therapies did not significantly reduce the risk of HER2-directed antibody-induced cardiotoxicity compared to control (RR 0.90).
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