Safety of Continuing Trastuzumab Despite Mild Cardiotoxicity

Darryl P. Leong, MBBS, MPH, MBiostat, PhD; Tammy Cosman, PhD; Muhammad M. Alhussein, MD; Nidhi Kumar Tyagi, MBChB; Sarah Karampatos, MS; Carly C. Barron, MD, MS; Douglas Wright, MD; Vikas Tandon, MD; Patrick Magloire, MD; Philip Joseph, MD; David Conen, MD, MPH; P.J. Devereaux, MD, PhD; Peter M. Ellis, MBBS, MMed, PhD; Som D. Mukherjee, MD, MS; Sukhbinder Dhesy-Thind, MD, MS

JACC. CardioOncology (Sep 2019)

Safety of Continuing Trastuzumab Despite Mild Cardiotoxicity

Darryl P. Leong, MBBS, MPH, MBiostat, PhD,
Tammy Cosman, PhD,
Muhammad M. Alhussein, MD,
Nidhi Kumar Tyagi, MBChB,
Sarah Karampatos, MS,
Carly C. Barron, MD, MS,
Douglas Wright, MD,
Vikas Tandon, MD,
Patrick Magloire, MD,
Philip Joseph, MD,
David Conen, MD, MPH,
P.J. Devereaux, MD, PhD,
Peter M. Ellis, MBBS, MMed, PhD,
Som D. Mukherjee, MD, MS,
Sukhbinder Dhesy-Thind, MD, MS

Affiliations

Darryl P. Leong, MBBS, MPH, MBiostat, PhD: Department of Medicine, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada; The Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada; Address for correspondence: Dr. Darryl P. Leong, C2-238 David Braley Building, Hamilton General Hospital, 237 Barton Street East, Hamilton, Ontario L8L 2X2, Canada.
Tammy Cosman, PhD: Department of Medicine, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada
Muhammad M. Alhussein, MD: Department of Medicine, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada
Nidhi Kumar Tyagi, MBChB: Department of Oncology, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada
Sarah Karampatos, MS: The Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada
Carly C. Barron, MD, MS: Department of Medicine, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada
Douglas Wright, MD: Department of Medicine, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada
Vikas Tandon, MD: Department of Medicine, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada
Patrick Magloire, MD: Department of Medicine, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada
Philip Joseph, MD: Department of Medicine, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada; The Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada
David Conen, MD, MPH: Department of Medicine, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada; The Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada
P.J. Devereaux, MD, PhD: Department of Medicine, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada; The Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
Peter M. Ellis, MBBS, MMed, PhD: Department of Oncology, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada
Som D. Mukherjee, MD, MS: Department of Oncology, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada
Sukhbinder Dhesy-Thind, MD, MS: Department of Oncology, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada

Journal volume & issue: Vol. 1, no. 1
pp. 1 – 10

Abstract

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Objectives: This study sought to evaluate the safety of continuing trastuzumab in patients with human epidermal growth factor receptor–positive breast cancer who developed mild cardiotoxicity. Background: Cardiotoxicity is the most common dose-limiting toxicity associated with trastuzumab. Current standard of care is discontinuation of trastuzumab, which can lead to worse cancer outcomes. It is unknown whether it is safe to continue trastuzumab despite mild cardiotoxicity. Methods: Patients were eligible for this phase I, prospective, single-arm trial if left ventricular ejection fraction (LVEF) was between 40% and the lower limit of normal or if it fell ≥15% from baseline. Participants were treated with angiotensin-converting enzyme (ACE) inhibitors and/or beta-blockers in a cardio-oncology clinic and were followed clinically and with serial echocardiograms for 1 year. The primary outcome was cardiac dose-limiting toxicity, defined as cardiovascular death, LVEF <40% together with any heart failure symptoms, or LVEF <35%. Results: All 20 participants received ACE inhibitors and/or beta-blockers. A total of 18 participants (90%) received all planned trastuzumab doses. Two (10%) participants developed cardiac dose-limiting toxicity (heart failure with LVEF <40%). Their LVEF and heart failure symptoms improved to nearly normal following permanent trastuzumab discontinuation. There were no deaths. LVEF rose progressively from a mean of 49% at enrollment to 55% at 12 months (p < 0.001). Conclusions: It may be feasible to continue trastuzumab despite mild cardiotoxicity in the setting of a cardio-oncology clinic, where ACE inhibitors and beta-blockers are administered. Approximately 10% of patients may develop moderate to severe heart failure using this approach. (Safety of Continuing Chemotherapy in Overt Left Ventricular Dysfunction Using Antibodies to Human Epidermal Growth Factor Receptor-2 [SCHOLAR]; NCT02907021)

Published in JACC. CardioOncology

ISSN: 2666-0873 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the circulatory (Cardiovascular) system; Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.journals.elsevier.com/jacc-cardiooncology

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