Adjuvant trastuzumab in HER2-positive breast cancer.

Dennis Slamon, Wolfgang Eiermann, Nicholas Robert, Tadeusz Pienkowski, Miguel Martin, Michael Press, John Mackey, John Glaspy, Arlene Chan, Marek Pawlicki, Tamas Pinter, Vicente Valero, Mei Ching Liu, Guido Sauter, Gunter von Minckwitz, Frances Visco, Valerie Bee, Marc Buyse, Belguendouz Bendahmane, Isabelle Tabah-FischMary Ann Lindsay, Alessandro Riva, John Crown, Cancer International Research Group Breast Cancer International Research Group

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1461 Citations (Scopus)

Abstract

Trastuzumab improves survival in the adjuvant treatment of HER-positive breast cancer, although combined therapy with anthracycline-based regimens has been associated with cardiac toxicity. We wanted to evaluate the efficacy and safety of a new nonanthracycline regimen with trastuzumab. We randomly assigned 3222 women with HER2-positive early-stage breast cancer to receive doxorubicin and cyclophosphamide followed by docetaxel every 3 weeks (AC-T), the same regimen plus 52 weeks of trastuzumab (AC-T plus trastuzumab), or docetaxel and carboplatin plus 52 weeks of trastuzumab (TCH). The primary study end point was disease-free survival. Secondary end points were overall survival and safety. At a median follow-up of 65 months, 656 events triggered this protocol-specified analysis. The estimated disease-free survival rates at 5 years were 75% among patients receiving AC-T, 84% among those receiving AC-T plus trastuzumab, and 81% among those receiving TCH. Estimated rates of overall survival were 87%, 92%, and 91%, respectively. No significant differences in efficacy (disease-free or overall survival) were found between the two trastuzumab regimens, whereas both were superior to AC-T. The rates of congestive heart failure and cardiac dysfunction were significantly higher in the group receiving AC-T plus trastuzumab than in the TCH group (P<0.001). Eight cases of acute leukemia were reported: seven in the groups receiving the anthracycline-based regimens and one in the TCH group subsequent to receiving an anthracycline outside the study. The addition of 1 year of adjuvant trastuzumab significantly improved disease-free and overall survival among women with HER2-positive breast cancer. The risk-benefit ratio favored the nonanthracycline TCH regimen over AC-T plus trastuzumab, given its similar efficacy, fewer acute toxic effects, and lower risks of cardiotoxicity and leukemia. (Funded by Sanofi-Aventis and Genentech; BCIRG-006 ClinicalTrials.gov number, NCT00021255.).

Original languageEnglish
Pages (from-to)1273-1283
Number of pages11
JournalThe New England journal of medicine
Volume365
Issue number14
DOIs
Publication statusPublished - Oct 6 2011

ASJC Scopus subject areas

  • Medicine(all)

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    Slamon, D., Eiermann, W., Robert, N., Pienkowski, T., Martin, M., Press, M., Mackey, J., Glaspy, J., Chan, A., Pawlicki, M., Pinter, T., Valero, V., Liu, M. C., Sauter, G., von Minckwitz, G., Visco, F., Bee, V., Buyse, M., Bendahmane, B., ... Breast Cancer International Research Group, C. I. R. G. (2011). Adjuvant trastuzumab in HER2-positive breast cancer. The New England journal of medicine, 365(14), 1273-1283. https://doi.org/10.1056/NEJMoa0910383