• Adjuvant/Neoadjuvant Therapy
• Breast Cancer
• Oncology Clinical Trials

The 2005 results of large randomized trials, including the Trastuzumab in Treating Women with Primary Breast Cancer [HERA; NCT00045032] trial, demonstrated statistically significant disease-free survival (DFS) benefit for 1 year of treatment with trastuzumab compared with observation in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. After 2005, the HERA trial focused on the secondary objective of comparing 2 years of trastuzumab treatment with 1 year of treatment. The results of this analysis were presented by Richard D. Gelber, MD, PhD, International Breast Cancer Study Group Statistical Center, Boston, Massachusetts, USA.

A total of 5102 patients with HER2-positive invasive early breast cancer were randomized after adjuvant treatment to observation (1698), 1 year of trastuzumab (n=1703), or 2 years of trastuzumab (n=1701). Patients in the observation group had the option to switch to trastuzumab in 2005. Patients included in the 2 years (n=1553) versus 1 year (n=1552) of trastuzumab analysis were those who remained disease-free for at least 366 days from randomization. For the safety analysis, primary cardiac events were defined as NYHA Class III/IV plus left ventricular ejection fraction (LVEF) <50% and ≥10% below baseline, or cardiac death. Secondary cardiac events were defined as LVEF <50% and ≥10% below baseline, excluding patients with a primary cardiac event.

At 8 years of median follow-up, DFS rates were 75.8% in the 2-year group versus 76.0% in the 1-year group (HR, 0.99; 95% CI, 0.85 to 1.14; p=0.86). DFS was not significantly different with 2 years versus 1 year of trastuzumab in either hormone receptor-positive (76.1% vs 77.2%; HR, 1.05; 95% CI, 0.85 to 1.29; p=0.67) or -negative (75.4% vs 74.7%; HR, 0.93; 95% CI, 0.76 to 1.14; p=0.51) patients. OS rates at 8 years of median follow-up were 86.4% with 2 years of treatment versus 87.6% with 1 year of treatment (HR, 1.05; 95% CI, 0.86 to 1.28; p=0.63).

In the safety analysis population, grade 3/4 adverse events (AEs) were reported in 20.4% of the 2-year group (n=1673), 16.3% of the 1-year group (n=1682), and 8.2% of the observation group (n=1744). Fatal AEs occurred in 1.2% of the 2-year group, 1.1% of the 1-year group, and 0.4% of the observation group. Primary cardiac events occurred in 1.0% of the 2-year group, 0.8% of the 1-year group, and 0.1% of the observation group. Secondary cardiac events occurred in 7.2% of the 2-year group, 4.1% of the 1-year group, and 0.9% of the observation group.

Results at median follow-up of 8 years also demonstrated sustained and statistically significant DFS and OS benefits with 1 year of trastuzumab treatment versus observation in the intention-to-treat analysis despite selective crossover.

The authors concluded that 2 years of treatment with trastuzumab did not provide long-term benefit compared with 1 year of treatment when administered as sequential treatment following chemotherapy. Cardiac toxicity and other AEs were increased in the 2-year treatment arm. The HERA results confirm that 1 year of trastuzumab treatment is the standard of care as part of adjuvant therapy for patients with HER2-positive early breast cancer.

• © 2012 MD Conference Express®