In the 11-year follow-up of the HERA trial reported in The Lancet, Cameron et al found that 1 year of trastuzumab (Herceptin) following adjuvant therapy for HER2-positive breast cancer remained associated with improved disease-free and overall survival compared with observation. No additional benefit was observed for 2 years of trastuzumab.
Study Details
In the phase III open-label HERA (BIG 1-01) trial, 5,102 women with HER2-positive early breast cancer from 39 countries were randomized between December 2001 and June 2005 to treatment with trastuzumab for 1 or 2 years or observation after completing all primary therapy (ie, surgery, chemotherapy, radiotherapy).
Trastuzumab was given at an initial dose of 8 mg/kg followed by 6 mg/kg once every 3 weeks. The primary endpoint for the current analysis was disease-free survival in the intent-to-treat population.
Disease-Free Survival
Among 5,099 patients included in the current analysis, 1,697 were in the observation group, 1,702 were in the 1-year trastuzumab group, and 1,700 were in the 2-year trastuzumab group. A total of 884 patients in the observation group (52%) crossed over to receive trastuzumab before a disease-free survival event after publication of the initial findings in the trial.
After a median follow-up of 11 years, both the 1-year trastuzumab group (hazard ratio [HR] = 0.76, 95% confidence interval [CI] = 0.68–0.86) and the 2-year trastuzumab group (HR = 0.77, 95% CI = 0.69–0.87) had significantly better disease-free survival vs the observation group. There was no difference in disease-free survival for 1 vs 2 years of trastuzumab (HR = 1.02, 95% CI = 0.89–1.17). Rates of 10-year disease-free survival were 69% in both trastuzumab groups and 63% in the observation group.
Overall survival was significantly improved in the 1-year trastuzumab group vs observation (HR = 0.74, 95% CI = 0.64–0.86). Survival rates at 12 years were 79% in the 1-year group, 80% in the 2-year group, and 73% in the observation group.
Cardiac Toxicity
Cardiac toxicity remained low in all groups and was primarily observed during the treatment phase. The incidence of secondary cardiac endpoints was 7.3% in the 2-year trastuzumab group, 4.4% in the 1-year group, and 0.9% in the observation group.
The investigators concluded: “One year of adjuvant trastuzumab after chemotherapy for patients with HER2-positive early breast cancer significantly improves long-term disease-free survival, compared with observation. Two years of trastuzumab had no additional benefit.”
The study was funded by F. Hoffmann-La Roche (Roche).
David Cameron, MD, of the University of Edinburgh Cancer Research Centre, is the corresponding author of The Lancet article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.