Cardiac outcomes of patients receiving adjuvant weekly paclitaxel and trastuzumab for node-negative, ERBB2-positive breast cancer Journal Article


Authors: Dang, C.; Guo, H.; Najita, J.; Yardley, D.; Marcom, K.; Albain, K.; Rugo, H.; Miller, K.; Ellis, M.; Shapira, I.; Wolff, A. C.; Carey, L. A.; Moy, B.; Groarke, J.; Moslehi, J.; Krop, I.; Burstein, H. J.; Hudis, C.; Winer, E. P.; Tolaney, S. M.
Article Title: Cardiac outcomes of patients receiving adjuvant weekly paclitaxel and trastuzumab for node-negative, ERBB2-positive breast cancer
Abstract: IMPORTANCE: Trastuzumab is a life-saving therapy but is associated with symptomatic and asymptomatic left ventricular ejection fraction (LVEF) decline. We report the cardiac toxic effects of a nonanthracycline and trastuzumab-based treatment for patients with early-stage human epidermal growth factor receptor 2 (ERBB2, formerly HER2 or HER2/neu)-positive breast cancer. OBJECTIVE: To determine the cardiac safety of paclitaxel with trastuzumab and the utility of LVEF monitoring in patients with node-negative, ERBB2-positive breast cancer. DESIGN, SETTING, AND PARTICIPANTS: In this secondary analysis of an uncontrolled, single group study across 14 medical centers, enrollment of 406 patients with node-negative, ERBB2-positive breast cancer 3 cm, or smaller, and baseline LVEF of greater than or equal to 50% occurred from October 9, 2007, to September 3, 2010. Patients with a micrometastasis in a lymph node were later allowed with a study amendment. Median patient age was 55 years, 118 (29%) had hypertension, and 30 (7%) had diabetes. Patients received adjuvant paclitaxel for 12 weeks with trastuzumab, and trastuzumab was continued for 1 year. Median follow-up was 4 years. INTERVENTIONS: Treatment consisted of weekly 80-mg/m2 doses of paclitaxel administered concurrently with trastuzumab intravenously for 12 weeks, followed by trastuzumab monotherapy for 39 weeks. During the monotherapy phase, trastuzumab could be administered weekly 2-mg/kg or every 3 weeks as 6-mg/kg. Radiation and hormone therapy were administered per standard guidelines after completion of the 12 weeks of chemotherapy. Patient LVEF was assessed at baseline, 12 weeks, 6 months, and 1 year. MAIN OUTCOMES AND MEASURES: Cardiac safety data, including grade 3 to 4 left ventricular systolic dysfunction (LVSD) and significant asymptomatic LVEF decline, as defined by our study, were reported. RESULTS: Overall, 2 patients (0.5%) (95% CI, 0.1%-1.8%) developed grade 3 LVSD and came off study, and 13 (3.2%) (95% CI, 1.9%-5.4%) had significant asymptomatic LVEF decline, 11 of whom completed study treatment. Median LVEF at baseline was 65%; 12 weeks, 64%; 6 months, 64%; and 1 year, 64%. CONCLUSIONS AND RELEVANCE: Cardiac toxic effects from paclitaxel with trastuzumab, manifesting as grade 3 or 4 LVSD or asymptomatic LVEF decline, were low. Patient LVEF was assessed at baseline, 12 weeks, 6 months, and 1 year, and our findings suggest that LVEF monitoring during trastuzumab therapy without anthracyclines could be simplified for many individuals.
Keywords: adult; treatment outcome; aged; aged, 80 and over; disease-free survival; middle aged; young adult; clinical trial; united states; pathophysiology; paclitaxel; disease free survival; chemotherapy, adjuvant; cancer staging; antineoplastic agent; neoplasm staging; metabolism; antineoplastic combined chemotherapy protocols; drug administration schedule; epidermal growth factor receptor 2; risk factors; enzymology; pathology; breast neoplasms; tumor marker; risk factor; time factors; risk assessment; multicenter study; adjuvant chemotherapy; diagnosis; receptor, erbb-2; drug administration; trastuzumab; heart stroke volume; stroke volume; ventricular function, left; erbb2 protein, human; heart left ventricle function; time factor; ventricular dysfunction, left; drug effects; very elderly; humans; human; female; antagonists and inhibitors; chemically induced; biomarkers, tumor
Journal Title: JAMA Oncology
Volume: 2
Issue: 1
ISSN: 2374-2437
Publisher: American Medical Association  
Date Published: 2016-01-01
Start Page: 29
End Page: 36
Language: English
DOI: 10.1001/jamaoncol.2015.3709
PUBMED: 26539793
PROVIDER: scopus
PMCID: PMC5654518
DOI/URL:
Notes: Article -- Export Date: 1 July 2016 -- Source: Scopus
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MSK Authors
  1. Clifford Hudis
    891 Hudis
  2. Chau Dang
    201 Dang