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Clinical Trial
. 2019 Jun;175(3):595-603.
doi: 10.1007/s10549-019-05191-2. Epub 2019 Mar 9.

Prospective evaluation of the cardiac safety of HER2-targeted therapies in patients with HER2-positive breast cancer and compromised heart function: the SAFE-HEaRt study

F Lynce  1 , A Barac  1   2 , X Geng  3 , C Dang  4   5 , A F Yu  4   5 , K L Smith  6   7 , C Gallagher  8 , P R Pohlmann  1 , R Nunes  6   7 , P Herbolsheimer  9 , R Warren  1 , M B Srichai  2   10 , M Hofmeyer  2 , A Cunningham  11 , P Timothee  11 , F M Asch  2   11 , A Shajahan-Haq  1 , M T Tan  3 , C Isaacs  1 , S M Swain  12
Affiliations
Clinical Trial

Prospective evaluation of the cardiac safety of HER2-targeted therapies in patients with HER2-positive breast cancer and compromised heart function: the SAFE-HEaRt study

F Lynce et al. Breast Cancer Res Treat. 2019 Jun.

Abstract

Purpose: HER2-targeted therapies have substantially improved the outcome of patients with breast cancer, however, they can be associated with cardiac toxicity. Guidelines recommend holding HER2-targeted therapies until resolution of cardiac dysfunction. SAFE-HEaRt is the first trial that prospectively tests whether these therapies can be safely administered without interruptions in patients with cardiac dysfunction.

Methods: Patients with stage I-IV HER2-positive breast cancer candidates for trastuzumab, pertuzumab or ado-trastuzumab emtansine (TDM-1), with left ventricular ejection fraction (LVEF) 40-49% and no symptoms of heart failure (HF) were enrolled. All patients underwent cardiology visits, serial echocardiograms and received beta blockers and ACE inhibitors unless contraindicated. The primary endpoint was completion of the planned HER2-targeted therapies without developing either a cardiac event (CE) defined as HF, myocardial infarction, arrhythmia or cardiac death or significant asymptomatic worsening of LVEF. The study was considered successful if planned oncology therapy completion rate was at least 30%.

Results: Of 31 enrolled patients, 30 were evaluable. Fifteen patients were treated with trastuzumab, 14 with trastuzumab and pertuzumab, and 2 with TDM-1. Mean LVEF was 45% at baseline and 46% at the end of treatment. Twenty-seven patients (90%) completed the planned HER2-targeted therapies. Two patients experienced a CE and 1 had an asymptomatic worsening of LVEF to ≤ 35%.

Conclusion: This study provides safety data of HER2-targeted therapies in patients with breast cancer and reduced LVEF while receiving cardioprotective medications and close cardiac monitoring. Our results demonstrate the importance of collaboration between cardiology and oncology providers to allow for delivery of optimal oncologic care to this unique population.

Keywords: Breast cancer; Cardiac dysfunction; Cardiac safety; Carvedilol; HER2-targeted therapy.

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Conflict of interest statement

F.L. reports personal fees from AstraZeneca, Celgene, Jounce; research grants to institution from Bristol-Myers Squibb, Calithera, Chugai, Genentech/Roche, Immunomedics, Inivata, Pfizer, Regeneron, Tesaro. C.D. reports personal fees from Amgen, Pfizer, Puma Biotechnology, Roche/Genentech; research grants from Amgen, Pfizer, Puma Biotechnology, Roche/Genentech. A.B. reports honoraria from Bristol-Myers Squibb. A.F.U. reports personal fees from Glenmark Pharmaceuticals. KLS reports ownership interest in AbbVie, Abbott Laboratories; honoraria from ASiM CME; research grants to self from Pfizer/NCCN and to institution from AstraZeneca, Pfizer, Galena BioPharma, Novartis, Pfizer, Syndax. P.R.P. reports ownership interest in Immunonet BioSciences; personal fees from Genentech/Roche, Heron Therapeutics, Immunonet BioSciences, OncoPlex Diagnostics, Personalized Cancer Therapy, Pfizer, Puma Biotechnology; research grants to institution from Advanced Cancer Therapeutics, Caris Centers of Excellence, Cascadian Therapeutics, Fabre-Kramer, Genentech/Roche, Pfizer, Pieris Pharmaceuticals; and payments for patents, royalties, or other intellectual property for U.S. Patent Nos. 8,486,413; 8,501,417; 9,023,362; and 294 9,745,377. R.N. reports personal fees from Bristol-Myers Squibb; travel and accommodation from Bristol-Myers Squibb, Caris Life Sciences. P.H. reports employment by AstraZeneca; C.I. reports honoraria from AstraZeneca, Genentech, Roche; personal fees from AstraZeneca, Genentech, NanoString Technologies, Novartis, Pfizer, Puma Biotechnology, Syndax; speakers’ bureau payments from AstraZeneca, Genentech, Pfizer; research grants to institution from Genentech, Novartis, Pfizer, Tesaro; and payments for patents, royalties, or other intellectual property from UpToDate, McGraw Hill. S.M.S. reports honoraria from Novartis, personal fees from Cardinal Health, Daiichi-Sankyo, Eli Lilly & Co., Genentech/Roche, Genomic Health, Inivata, Peiris Pharmaceuticals, Tocagen; research grants to institution from Genentech; travel and accommodation from Caris Centers of Excellence, Daiichi-Sankyo, Eli Lilly & Co., Genentech/Roche, NanoString Technologies; payments for participation on OlympiA IDMC from AstraZeneca. All remaining authors have declared no conflicts of interest.

Figures

Fig. 1
Fig. 1
Patient disposition on the SAFE-HEaRt study
Fig. 2
Fig. 2
a Left ventricular ejection fraction (LVEF) variations during treatment. b LVEF at baseline, end of treatment (EOT) and 6 months later (Post-EOT). Abbreviations: W0 week 0, W6 week 6, W12 week 12, W24 week 24, W36 week 36; W48 week 48, SD Standard deviation
Fig. 3
Fig. 3
Cardiac event (CE) or asymptomatic decline of left ventricular ejection fraction (LVEF) in the study population
See this image and copyright information in PMC

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