- Paper Report
- Open Access
Phase III trial of chemotherapy ? HerceptinR in metastatic breast cancer
- Fatima Cardoso1
© Biomed Central Ltd 2001
- Received: 27 April 2001
- Accepted: 20 August 2001
- Published: 1 December 2001
- Breast cancer, Herceptin, HER2, phase III trial
Despite advances in diagnosis and treatment, breast cancer still remains a major cause of cancer deaths. Metastatic breast cancer (MBC) is virtually incurable, with median survival of 18 to 24 months. The HER2 gene encodes a growth factor membrane receptor that is overexpressed in 25-30% of MBC cases and is associated with aggressive metastasis and poor prognosis. Transtuzumab (HerceptinR) is a humanised monoclonal antibody against HER2 that has proven efficacy as a single-agent therapeutic for MBC. This randomised phase III trial analysed the effect of adding transtuzumab to standard first-line chemotherapy (CT) for MBC.
In an intention-to-treat analysis, the addition of transtuzumab was associated with statistically significant and better results for time to disease progression (7.4 months versus 4.6 months; P <0.001), response rate (50% versus 32%; P <0.001), duration of response (9.1 months versus 6.1 months; P <0.001) and overall survival (25.1 months versus 20.3 months; P = 0.046). Similar differences were seen in both chemotherapy subgroups (anthracycline-based and paclitaxel), although for overall survival the Pvalues were 0.16 and 0.17, respectively. Addition of transtuzumab was also associated with higher cardiotoxicity than that for CT alone, particularly in the anthracycline-based subgroup and in patients who had received adjuvant anthracyclines. After a median follow-up of 30 months the authors concluded that transtuzumab increases the clinical benefit of first-line CT in MBC and reduces the relative risk of death by 20%.
Immunohistochemical IHC analysis of HER2 positivity, randomised phase III clinical trial, intention-to-treat analysis, Kaplan-Meier and two-sided log-rank tests
- Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eirmann W, Wolter J, Pegram M, Baselga J, Norton L: Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. New Engl J Med . 2001, 344: 783-792.View ArticlePubMedGoogle Scholar