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Heart Failure Therapies for the Prevention of HER2-Monoclonal Antibody-Mediated Cardiotoxicity: A Systematic Review and Meta-Analysis of Randomized Trials


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.

Type Journal
ISBN 2072-6694 (Print) 2072-6694 (Linking)
Authors Brown, L. J.; Meredith, T.; Yu, J.; Patel, A.; Neal, B.; Arnott, C.; Lim, E.
Responsible Garvan Author (missing name)
Publisher Name Cancers (Basel)
Published Date 2021-11-30
Published Volume 13
Published Issue 21
Published Pages 5527
Status Published in-print
DOI 10.3390/cancers13215527
URL link to publisher's version