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Spotlight on Trastuzumab in Metastatic Breast Cancer Overexpressing HER2

  • Adis Spotlight
  • Published:
American Journal of Cancer

Abstract

Trastuzumab is a humanized monoclonal antibody developed to target the HER2 receptor which is over-expressed by some cancer cells, including 25 to 30% of breast cancers. Binding with high affinity to the extracellular domain of HER2, trastuzumab inhibits the proliferation of tumor cells that overexpress HER2.

A large well designed multicenter study found that the addition of trastuzumab to either an anthracycline plus cyclophosphamide or to paclitaxel, as first-line therapy for metastatic breast cancer overexpressing the HER2 receptor, significantly increased time to disease progression, rate of objective response, duration of response and survival compared with chemotherapy alone.

Single-agent trastuzumab was associated with an objective response in 15% of extensively pretreated patients with metastatic breast cancer overexpressing HER2, and 26% of previously untreated patients. Patients with a HER2 overexpression level of 3+ using immunohistochemical assay, or a positive HER2 result using fluorescence in situ hybridisation, benefit more from trastuzumab therapy than those with tumors overexpressing at a level of 2+.

Trastuzumab has demonstrated synergistic action with several chemotherapy agents preclinically but the optimal combination clinically is yet to be determined.

Trastuzumab is generally well tolerated by most patients; the most significant adverse effects being acute fever and/or chills and the potential to cause cardiac dysfunction. Serious adverse events, including anaphylaxis and death, have occurred in 0.25% of patients.

Symptomatic or asymptomatic cardiac dysfunction occurred in 27% of patients receiving an anthracycline and cyclophosphamide combined with trastuzumab. Thus, combination therapy with anthracyclines is not recommended. Symptomatic or asymptomatic cardiac dysfunction occurred in 13% of patients receiving trastuzumab plus paclitaxel and in 4.7% of patients receiving trastuzumab alone.

In conclusion, intravenous trastuzumab is effective as a single-agent, and in combination with chemotherapy it significantly improves the median time to disease progression and survival time in patients with metastatic breast cancer overexpressing the HER2 receptor compared with chemotherapy alone. Cardiotoxicity is the main concern with therapy; particularly in patients with pre-existing cardiac dysfunction, the elderly and in combination with, or following, anthracyclines. Trastuzumab is indicated for use with paclitaxel as first-line therapy or as a single agent in second- or third-line treatment regimens for patients with metastatic breast cancer overexpressing HER2. Investigation is ongoing to ascertain the optimal combination regimen containing trastuzumab and antineoplastic agents. In addition, current research is focusing on the optimal timing, sequencing and duration of therapy as well as administration in the neoadjuvant and adjuvant setting.

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Acknowledgements

The full text of this article appeared in Drugs 2002; 62 (1): 209-243, and was reviewed by: N. Bangemann, Medical Center Benjamin Franklin, Free University, Berlin, Germany; H. Burstein, Dana-Faber Cancer Institute, Boston, Massachussetts, USA; L. A. Carey, UNC Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA; I. O. Ellis, Department of Histopathology, City Hospital, Nottingham, England; V. Harvey, Department of Clinical Oncology, Auckland Hospital, Auckland, New Zealand; J. Horton, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, USA; B. Leyland-Jones, Department of Oncology, McGill University, Montreal, Canada; R. Seshadri, Flinders Medical Centre, Bedford Park, South Australia, Australia.

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    Kate McKeage & Caroline M. Perry

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  1. Kate McKeage
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Correspondence to Kate McKeage.

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The full text of this article was published in Drugs 2002; 62 (1): 209–243.

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McKeage, K., Perry, C.M. Spotlight on Trastuzumab in Metastatic Breast Cancer Overexpressing HER2. Am J Cancer 1, 217–221 (2002). https://doi.org/10.2165/00024669-200201030-00006

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