One year of therapy with Herceptin® (trastuzumab) appears to be optimal in the adjuvant setting for women diagnosed with HER2-positive early breast cancer, according to the results of two studies presented at the ESMO 2012 Congress of the European Society for Medical Oncology in Vienna.
The HER2 pathway is a biological pathway involved in cellular replication and growth. Approximately 20-25% of breast cancers overexpress the HER2 protein and are referred to as HER2-positive. Herceptin targets and blocks the HER2-protein, and is used for the treatment of both early-stage and more advanced HER2-positive breast cancer.
One year of Herceptin is considered standard treatment for patients with HER2-positive early breast cancer and has been shown to significantly improve disease-free survival and overall survival. In the two studies presented at ESMO, researchers evaluated whether shorter or longer durations of Herceptin treatment would improve or hinder outcomes.
The HERA Trial
Started in 2001, the HERA trial is an international, multi-center, phase III randomized study that includes 5,102 women with early HER2-positive breast cancer. After finishing primary therapy with surgery, chemotherapy, and radiation, the women in the study were randomly assigned to observation or Herceptin every three weeks for one year or two years.
Now, landmark results from the study show that extending Herceptin for two years does not significantly improve outcomes. Overall survival in the two groups was comparable, as was disease free survival. What’s more—the study served to confirm previous data that indicated Herceptin’s benefit in this population. After eight years of median follow-up, the durable benefit in disease-free survival and overall survival of one year of Herceptin compared to no Herceptin remained stable—indicating that the benefit of Herceptin lasts over years.
The results serve as confirmation and reassurance—one year of Herceptin is the optimal dose to prevent disease recurrence. Less is not enough and more is not better.
The PHARE Trial
Although one year of Herceptin has been shown to provide a survival benefit to patients with HER2-positive, early breast cancer, there have been concerns about cardiac toxicity.
The PHARE trial was a randomized, non-inferiority trial conducted by the French National Cancer Institute (INCa) to compare six months of Herceptin to the standard of one year. The study involved 3,382 patients at 150 cancer centers in France. The primary objective was to compare disease-free survival among patients who received six months of Herceptin versus those who received one year. Secondary objectives included overall survival and cardiac toxicity.
After a median follow-up of 42.5 months, the study could not conclude that 6 months is as good as a year. If anything, there was a trend towards fewer recurrence and deaths for women who took a year of treatment.
 Gelber RD, Goldhirsch A, Piccart M, et al. HERA TRIAL: 2 years versus 1 year of trastuzumab after adjuvant chemotherapy in women with HER2-positive early breast cancer at 8 years of median follow up. Presented at the 37th Congress of the European Society for Medical Oncology (ESMO), Vienna, Austria, September 28-October 2, 2012. Abstract LBA6.
 Pivot X, Romieu G, Bonnefoi H, et al. PHARE Trial results comparing 6 to 12 months of trastuzumab in adjuvant early breast cancer. Presented at the 37th Congress of the European Society for Medical Oncology (ESMO), Vienna, Austria, September 28-October 2, 2012. Abstract LBA5.
Posted October 3, 2012