The use of trastuzumab in the treatment of early breast cancer: results from the HERA trial  

 

The overexpression of HER-2, a transmembrane protein with tyrosine kinase activity, in 20 % to 30 % of breast cancers (BC) is associated with a greater risk for disease progression and death. The humanised antibody trastuzumab (Herceptin®), designed to target and block the function of HER-2, has been shown to improve time to progression and overall survival in the metastatic setting, when given in combination with chemotherapy (CT). Five randomised trials have recently investigated the role of trastuzumab in early breast cancer. More than 14,000 patients with node positive or high risk node negative, HER-2 overexpressing tumours were recruited worldwide. The results are highly consistent, with an impressive 39% to 52% reduction in the risk of recurrence at median follow-up periods ranging from 12 to 36 months.

The international HERA (HERceptin Adjuvant) trial enrolled nearly 5,100 HER-2 positive early BC patients at 480 sites in 39 countries across the world. In this study’s 3-arm design, trastuzumab administered every 3 weeks after completion of CT for either 1 or 2 years was compared with an observation arm. According to the first analysis, at a median follow-up of one year, the primary efficacy endpoint was met: patients who received one year of trastuzumab had a statistically significant improvement in disease-free survival (HR 0.54; p<0.0001). This impressive decrease of early recurrences at distant sites prompted the release of the results at an unusually short follow-up time. As expected, overall survival had not yet reached statistical significance. The cumulative incidence of severe cardiac events was very low (0.5% in the trastuzumab arm vs. 0% in the observation arm). The comparison between the one-year and two-year arms may be available by 2008 or earlier.

In contrast to the other trials of adjuvant trastuzumab, the results of the HERA study are widely applicable, as a considerable range of adjuvant CT regimens were used prior to treatment with trastuzumab.

   

Bibliographical reference:

Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. "Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer", N Eng J Med 2005; 353:1659-72.  

 

Daniela D. Rosa, Lissandra Dal Lago, Chantal Bernard and Martine J. Piccart

Medicine Department, Jules Bordet Institute, Brussels, Belgium