Cardiac Outcomes of Patients Receiving Adjuvant Weekly Paclitaxel and Trastuzumab for Node-Negative, ERBB2-Positive Breast Cancer.

Dang C, Guo H, Najita J, Yardley D, Marcom K, Albain K, Rugo H, Miller K, Ellis M, Shapira I, Wolff AC, Carey LA, Moy B, Groarke J, Moslehi J, Krop I, Burstein HJ, Hudis C, Winer EP, Tolaney SM
JAMA Oncol. 2016 2 (1): 29-36

PMID: 26539793 · PMCID: PMC5654518 · DOI:10.1001/jamaoncol.2015.3709

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.

MeSH Terms (25)

Adult Aged Aged, 80 and over Antineoplastic Combined Chemotherapy Protocols Biomarkers, Tumor Breast Neoplasms Chemotherapy, Adjuvant Disease-Free Survival Drug Administration Schedule Female Humans Middle Aged Neoplasm Staging Paclitaxel Receptor, ErbB-2 Risk Assessment Risk Factors Stroke Volume Time Factors Trastuzumab Treatment Outcome United States Ventricular Dysfunction, Left Ventricular Function, Left Young Adult

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