Cardiac safety of paclitaxel plus trastuzumab and pertuzumab in patients with HER2-positivemetastatic breast cancer

Anthony F. Yu, Carlos Manrique, Shawn Pun, Jennifer E. Liu, Elton Mara, Martin Fleisher, Sujata Patil, Lee W. Jones, Richard M. Steingart, Clifford A. Hudis, Chau T. Dang

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Introduction. Myocardial strain imaging and blood biomarkers have been proposed as adjuncts to left ventricular ejection fraction (LVEF) monitoring for the early detection of cardiotoxicityduring cancertherapy.Wereport theresults ofapreplanned cardiac safety analysis of global longitudinal strain (GLS), and troponin-I (TnI) and brain natriuretic peptide (BNP) levels in the phase II study of paclitaxel, trastuzumab, and pertuzumab (THP) formetastatic HER2-positive breast cancer. Patients and Methods. Patients with 0–1 lines of prior therapy were treated with weekly paclitaxel (80 mg/m2) plus trastuzumab (8 mg/kg loading dose followed by 6 mg/kg) and pertuzumab (840 mg loading dose followed by 420 mg) every 3 weeks. Exploratory endpoints were GLS measured with speckle-tracking echocardiography every 3months and TnI and BNP levels measured every 6 weeks (immediately pre- and postchemotherapy infusion) at 6 time points. Results. Sixty-seven of 69 enrolled patients were treated with THP: 19 (28%) had hypertension, 8 (12%) had diabetes, 11 (16%) had hyperlipidemia, and 26 (38%) had smoking history. After a median follow-up of 21 months (range: 3–38 months), no patients developed symptomatic heart failure. Two patients (3.0%) experienced asymptomatic LVEF decline (grade 2). The mean GLS (±SD) was 19%±2% (baseline), 19%±2% (month 6), and 19%±3% (month 12). Detectable TnI (>0.06 ng/mL) and elevated BNP (>100 pg/mL) levels were observed in 3 (4.3%) and 2 (3.0%) patients, respectively, but were not associated with LVEF decline. Conclusion. The absence of any significant changes in GLS and cardiac biomarkers (TnI and BNP) further support the cardiac safety of THP in patients with metastatic HER2-positive breast cancer.

Original languageEnglish (US)
Pages (from-to)418-424
Number of pages7
JournalOncologist
Volume21
Issue number4
DOIs
StatePublished - Apr 1 2016

Keywords

  • Biomarkers
  • Cardiotoxicity
  • Heart failure
  • Imaging
  • Pertuzumab
  • Trastuzumab

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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