• Oncology Genomics
• Breast Cancer
• Oncology Clinical Trials

In 2005, data from 3 large randomized trials demonstrated that 1 year of trastuzumab treatment provided a statistically significant disease-free survival (DFS) benefit compared with no trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer [Piccart-Gebhart MJ et al. N Engl J Med 2005]. One of these studies, the Trastuzumab in Treating Women with Primary Breast Cancer [HERceptin Adjuvant (HERA); NCT00045032] trial, continued trastuzumab therapy to assess whether 2 years of treatment was superior to 1 year. Martine J. Piccart-Gebhart, MD, PhD, Jules Bordet Institute, Brussels, Belgium, provided an update of the HERA trial after 8 years of median follow-up.

Women with locally determined and centrally confirmed early HER2-positive invasive breast cancer who had undergone surgery and neoadjuvant chemotherapy with or without radiation therapy were recruited globally except in the United States (n=5102). Patients were randomized to observation, 1 year of trastuzumab every 3 weeks, or 2 years of trastuzumab every 3 weeks. Patients in the observation arm were given the option of crossing over after the release of first results in 2005.

No significant difference was found in DFS or overall survival (OS) between the 2- and 1-year trastuzumab arms at 8 years median follow-up. When patients were stratified by receptor status, DFS and OS were still similar between the 2- and 1-year groups. At the interim point of 4 years median follow-up, a transient DFS advantage was reported for patients with hormone receptor (HR)-negative breast cancer who received 2 years of trastuzumab compared with 1 year of treatment in patients with HR-negative breast cancer. However, this benefit was not sustained at 8 years median follow-up.

Although no differences in DFS and OS were observed between 2 years of trastuzumab and 1 year, secondary cardiac endpoints and other grade 3 or 4 adverse events were increased in the arm treated with trastuzumab for 2 years. Nonetheless, most cardiac endpoints were reversible and occurred during the treatment administration period.

Prof. Piccart-Gebhart said, “There is no evidence of long-term benefit of 2 years compared with 1 year trastuzumab when administered as sequential treatment following chemotherapy.” She added that “transient DFS advantage for the 2-year arm in the hormone receptor-negative cohort [at 4 years follow-up] highlights the need for long-term follow-up in trials investigating different durations of adjuvant trastuzumab.”

After disclosure of the first results in 2005, 885 of the 1698 patients (52.1%) crossed over to receive trastuzumab, which complicates long-term follow-up results. For the analysis of DFS and OS for 1 year trastuzumab versus observation at 8 years median follow-up, the HERA results show sustained statistically significant benefit for DFS and OS compared with observation in intention-to-treat analyses despite selective crossover. In addition, benefit was shown across HR-positive and HR-negative cohorts at 8 years median follow-up.

Prof. Piccart-Gebhart concluded, “One year of trastuzumab remains the standard of care as part of an adjuvant therapy for patients with HER2-positive early breast cancer.”

• © 2013 MD Conference Express®