11-Year Follow-up of Adjuvant Trastuzumab in the HERA Trial


Key Points

  • At 11-year follow-up, randomization to 1 year of trastuzumab was associated with prolonged disease-free and overall survival compared with randomization to observation in patients with HER2-positive breast cancer.
  • Two years of trastuzumab provided no additional benefit over one year of treatment.

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.

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