Long-term cardiac tolerability of trastuzumab in metastatic breast cancer: The M.D. Anderson Cancer Center experience

Valentina Guarneri, Daniel J. Lenihan, Vicente Valero, Jean Bernard Durand, Kristine Broglio, Kenneth R. Hess, Laura Boehnke Michaud, Ana M. Gonzalez-Angulo, Gabriel N. Hortobagyi, Francisco J. Esteva

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278 Scopus citations

Abstract

Purpose: To evaluate the cardiac safety of long-term trastuzumab therapy in patients with human epidermal growth receptor 2 (HER2) - overexpressing metastatic breast cancer (MBC) treated at The University of Texas M.D. Anderson Cancer Center (Houston, TX). Patients and Methods: Among 218 MBC patients treated with trastuzumab-based therapy for at least 1 year, 173 patients were assessable for cardiac toxicity. Cardiac events (CEs) were defined as follows: asymptomatic decrease of left ventricular ejection fraction (LVEF) below 50%; decrease of 20 percentage points in LVEF compared with the baseline; or signs or symptoms of congestive heart failure (CHF). Results: The median cumulative time for trastuzumab administration was 21.3 months. The median follow-up was 32.6 months (range, 11.8 to 79.0 months). Forty-nine patients (28%) experienced a CE: three patients (1.7%) had an asymptomatic decrease in the LVEF of 20 percentage points, 27 patients (15.6%) experienced grade 2 cardiac toxicity, and 19 patients (10.9%) experienced grade 3 cardiac toxicity. All but three patients had improved LVEF or symptoms of CHF with trastuzumab discontinuation and appropriate therapy. There was one cardiac-related death (0.5%). Baseline LVEF was significantly associated with CE (hazard ratio, 0.94; P = .001). The hazard of a CE among patients taking concomitant taxanes was higher early in the follow-up period but declined during the course of follow-up. Conclusion: The risk of cardiac toxicity of long-term trastuzumab-based therapy is acceptable in this population, and this toxicity is reversible in the majority of the patients. In patients who have experienced a CE, additional treatment with trastuzumab can be considered after recovery of cardiac function.

Original languageEnglish
Pages (from-to)4107-4115
Number of pages9
JournalJournal of Clinical Oncology
Volume24
Issue number25
DOIs
StatePublished - Sep 1 2006
Externally publishedYes

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    Guarneri, V., Lenihan, D. J., Valero, V., Durand, J. B., Broglio, K., Hess, K. R., Michaud, L. B., Gonzalez-Angulo, A. M., Hortobagyi, G. N., & Esteva, F. J. (2006). Long-term cardiac tolerability of trastuzumab in metastatic breast cancer: The M.D. Anderson Cancer Center experience. Journal of Clinical Oncology, 24(25), 4107-4115. https://doi.org/10.1200/JCO.2005.04.9551