e-Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2021

Heart failure therapies for the prevention of HER2-monoclonal antibody mediated cardiotoxicity: a systematic review and meta-analysis. (#219)

Lauren J Brown 1 2 , Thomas Meredith 3 4 5 , Jie Yu 6 , Anushka Patel 6 , Bruce Neal 6 7 , Clare Arnott 6 8 , Elgene Lim 1 2 5
  1. The Garvan Institute, Sydney
  2. The Kinghorn Cancer Centre, St Vincent's Hospital, Darlinghurst
  3. Cardiology Department , St Vincent's Hospital, Darlinghurst
  4. Victor Chang Cardiac Research Institute, Sydney
  5. University of New South Wales, Sydney
  6. The George Institute for Global Health, University of New South Wales, Sydney
  7. Imperial College, London, United Kingdom
  8. Royal Prince Alfred Hospital, Sydney

Background: Monoclonal antibodies, including trastuzumab, pertuzumab and antibody-drug conjugates, form the backbone of systemic management of early and metastatic HER2-positive breast cancer. These are associated with cardiotoxicity in pivotal trials. While the assessment of left ventricular function (LVEF) prior to and during HER2-directed antibody treatment is recommended, there are currently no guidelines for the prevention of cardiotoxicity.

Aims/Methods: We performed a systematic review and meta-analysis of randomized controlled trials evaluating the efficacy of therapy for the prevention of monoclonal antibody-induced cardiotoxicity in patients with breast cancer. The primary outcome was an absolute reduction in LVEF of ≥ 10% or drop in LVEF to ≤ 50%.  Key secondary outcomes were the need for interruption of monoclonal antibody therapy and mean change in LVEF. Effects were determined by calculating risk ratios (RRs) and 95% confidence intervals (95% CI) or weighted mean differences (WMD) using random-effects models. 

Results: We identified five eligible trials; two studied the effects of an angiotensin-converting enzyme (ACE) inhibitor, one the effects of an angiotensin-II-receptor blocker (ARB) and four the effects of a beta-blocker.  Three trials (n=952) reported data about the primary outcome with no effect on risk of cardiotoxicity 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/ARB and beta-blockade (p homogeneity=0.50). Active treatment reduced the risk of trastuzumab interruptions (RR=0.57, 95%CI 0.43 to 0.77, p=0.0002) with similar findings for ACE/ARB and beta-blockade (p homogeneity=0.97).  There was protection against LVEF decline (WMD -1.5%, 95%CI -2.16 to -0.83, p=<0.00001) with both ACE/ARB and beta-blockers (p homogeneity=0.73).

Conclusions: Prophylactic treatment with ACE/ARB or beta-blocker therapy may be of value for preventing treatment interruption amongst patients with breast cancer prescribed monoclonal antibodies.  An adequately powered randomized trial is required to define the role of routine prophylactic cardio-protection amongst this patient group.