Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer.

Abstract

BACKGROUND:

Trastuzumab, a recombinant monoclonal antibody against HER2, has clinical activity in advanced breast cancer that overexpresses HER2. We investigated its efficacy and safety after excision of early-stage breast cancer and completion of chemotherapy.

METHODS:

This international, multicenter, randomized trial compared one or two years of trastuzumab given every three weeks with observation in patients with HER2-positive and either node-negative or node-positive breast cancer who had completed locoregional therapy and at least four cycles of neoadjuvant or adjuvant chemotherapy.

RESULTS:

Data were available for 1694 women randomly assigned to two years of treatment with trastuzumab, 1694 women assigned to one year of trastuzumab, and 1693 women assigned to observation. We report here the results only of treatment with trastuzumab for one year or observation. At the first planned interim analysis (median follow-up of one year), 347 events (recurrence of breast cancer, contralateral breast cancer, second nonbreast malignant disease, or death) were observed: 127 events in the trastuzumab group and 220 in the observation group. The unadjusted hazard ratio for an event in the trastuzumab group, as compared with the observation group, was 0.54 (95 percent confidence interval, 0.43 to 0.67; P<0.0001 by the log-rank test, crossing the interim analysis boundary), representing an absolute benefit in terms of disease-free survival at two years of 8.4 percentage points. Overall survival in the two groups was not significantly different (29 deaths with trastuzumab vs. 37 with observation). Severe cardiotoxicity developed in 0.5 percent of the women who were treated with trastuzumab.

CONCLUSIONS:

One year of treatment with trastuzumab after adjuvant chemotherapy significantly improves disease-free survival among women with HER2-positive breast cancer. (ClinicalTrials.gov number, NCT00045032.)

• Authors: Martine J Piccart-Gebhart, Marion Procter, Brian Leyland-Jones, Aron Goldhirsch, Michael Untch, Ian Smith, Luca Gianni, Jose Baselga, Richard Bell, Christian Jackisch, David Cameron, Mitch Dowsett, Carlos H Barrios, Günther Steger, Chiun-Shen Huang, Michael Andersson, Moshe Inbar, Mikhail Lichinitser, István Láng, Ulrike Nitz, Hiroji Iwata, Christoph Thomssen, Caroline Lohrisch, Thomas M Suter, Josef Rüschoff, Tamás Suto, Victoria Greatorex, Carol Ward, Carolyn Straehle, Eleanor McFadden, M Stella Dolci, Richard D Gelber, Herceptin Adjuvant (HERA) Trial Study Team
• Journal: The New England journal of medicine (N Engl J Med) Vol. 353 Issue 16 Pg. 1659-72 (Oct 20 2005) ISSN: 1533-4406 [Electronic] United States
• PMID: 16236737 (Publication Type: Clinical Trial, Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2005 Massachusetts Medical Society.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents
• Receptor, ErbB-2
• Trastuzumab

Topics

• Adult
• Antibodies, Monoclonal (adverse effects, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents (adverse effects, therapeutic use)
• Breast Neoplasms (drug therapy, mortality, radiotherapy, surgery)
• Chemotherapy, Adjuvant
• Combined Modality Therapy
• Disease-Free Survival
• Female
• Heart Diseases (chemically induced)
• Humans
• Middle Aged
• Receptor, ErbB-2 (analysis)
• Recurrence
• Survival Analysis
• Trastuzumab