S25 Update of the HERA trial and the role of 1 year Trastuzumab as adjuvant therapy for breast cancer

Background: Trastuzumab, a recombinant monoclonal antibody against the HER-2 receptor, has been shown to significantly improve disease-free and overall survival in women with HER-2 positive early breast cancer when given concurrently with or sequentially after chemotherapy. Materials and Methods: HERA is an ongoing international, multicenter, randomised phase III trial comparing one or two years of adjuvant trastuzumab given every three weeks with observation in 5,102 patients with HER-2 positive either node-negative (tumour size 1.0 cm) or nodepositive early breast cancer who had completed locoregional therapy and had received at least four cycles of standard neoadjuvant or adjuvant chemotherapy. Central confirmation of HER-2 positivity and LVEF 55% after completing chemotherapy and radiotherapy were required prior to randomisation. The second planned interim analysis of the 1 yr vs 2 yr trastuzumab comparison in the HERA trial was conducted on October 20, 2008. The Independent Data Monitoring Committee (IDMC) recommended that the study continue as planned without disclosing data on the 2 yr trastuzumab group. In the observation and the 1 yr trastuzumab groups, 827 disease-free survival events (DFS) have been observed at a median follow up of 48.4 months after randomization, and are the subject to the present update. Results: After release of the HERA and the combined B31 and N9831 results in 2005, a protocol amendment allowed for eligible observation patients to receive trastuzumab and data were continuously collected. Out of the 1698 observation patients, there were 885 observation patients who crossed over to trastuzumab. These late starter patients started trastuzumab at a median of 22.8 months (<1−52.7) from randomization. The updated intent-to-treat (ITT) analysis of DFS confirmed a statistically significant benefit in favour of the patients who received 1 yr of trastuzumab following chemotherapy compared with observation (p < 0.0001). Additional analyses to examine the effect of the late start of trastuzumab in the observation group and the influence of the selective crossover on the treatment comparison will be presented. Conclusion: The updated analysis of the HERA trial confirmed the benefit of delivering adjuvant trastuzumab for 1 yr after chemotherapy in women with HER2-positive tumors despite the substantive crossover of observation group patients to active treatment. The HERA study is ongoing and final results including the comparison of 1 yr vs 2 yrs trastuzumab are expected in 2011.