Cardiac safety of paclitaxel plus trastuzumab and pertuzumab in patients with HER2-positive metastatic breast cancer Journal Article


Authors: Yu, A. F.; Manrique, C.; Pun, S.; Liu, J. E.; Mara, E.; Fleisher, M.; Patil, S.; Jones, L. W.; Steingart, R. M.; Hudis, C. A.; Dang, C. T.
Article Title: Cardiac safety of paclitaxel plus trastuzumab and pertuzumab in patients with HER2-positive metastatic breast cancer
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. © AlphaMed Press 2016.
Keywords: biomarkers; heart failure; cardiotoxicity; imaging; trastuzumab; pertuzumab
Journal Title: The Oncologist
Volume: 21
Issue: 4
ISSN: 1083-7159
Publisher: AlphaMed Press  
Date Published: 2016-04-01
Start Page: 418
End Page: 424
Language: English
DOI: 10.1634/theoncologist.2015-0321
PROVIDER: scopus
PUBMED: 26984450
PMCID: PMC4828117
DOI/URL:
Notes: Article -- Export Date: 2 May 2016 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Sujata Patil
    386 Patil
  2. Jennifer Liu
    37 Liu
  3. Clifford Hudis
    846 Hudis
  4. Chau Dang
    159 Dang
  5. Richard M Steingart
    115 Steingart
  6. Martin Fleisher
    241 Fleisher
  7. Anthony Yu
    35 Yu
  8. Lee Winston Jones
    107 Jones
  9. Shawn Clinton Pun
    9 Pun
  10. Elton   Mara
    2 Mara