Carolyn Vachani, RN, MSN, AOCN
Abramson Cancer Center of the University of Pennsylvania
Last Modified: November 11, 2005
Presented by: Tamsin Mulrooney, PhD(c), MS, ARNP, OCN, Norris Cotton Cancer Center at Dartmouth Hitchcock Medical Center
Tammy presented the data, recently discussed at ASCO 2005 and published in the New England Journal of Medicine, that many clinicians called stunning and predicted will transform the way many women with breast cancer are treated. Trastuzumab (Herceptin) is a monoclonal antibody that targets the HER2/neu receptor, which points to a more aggressive disease and is found in 20-50% of breast cancers. Trastuzumab (tras) is currently approved for use in metastatic breast cancer, as first line therapy in combination with paclitaxel or as a single agent, third line. The studies presented here included early stage breast cancer patients, with and without node- positive disease.
The first is a combination of two trials that were essentially looking at the same question – NSABP (B31) and NCCT (N9831). The data was based on an interim analysis that led the investigators to halt the trial, allowing those who were not receiving tras to do so. The 3300 patients received doxorubicin and cyclophosphamide (AC), followed by paclitaxel with or without tras. NCCTG also included an arm that received the tras after the completion of 12 weeks of weekly taxol to see if there was a benefit based on sequencing. Due to the concerns of heart failure, only those women with normal ejection fractions (EF) were permitted to enroll and function was checked periodically throughout the trial, with holding of the drug if the EF dropped by 10-15% from baseline.
The results at three years follow-up for disease-free survival (DFS) favored the AC + paclitaxel with tras, with a 52% reduction in recurrence (p value of 3x 10 to the -12). In addition, distant recurrence was decreased by 53%, and appears to decrease even further over time. Overall survival was improved by 33% (p= 0.015). The arm that received tras after completion of paclitaxel did not have a statistically significant improved DFS over the control arm. The study did not find a significant improvement in DFS in the node-negative subset, but this is probably due to the small numbers of women in this category. Clearly, more research is needed in this group. As far as the cardiac effects, the study reported a 4% incidence of cardiac toxicity. It is important to keep in mind that the patients were very closely monitored for cardiac events, allowing early detection of decreases in EF.
The second study, entitled HERA, was conducted in Europe and Australia . The trial participants received standard therapy followed by either observation, tras for 1 year, or tras for 2 years. The interim analysis presented the observation arm vs. tras for 1 year. The third arm results will not be available until 2008. Results at the median 1 year follow-up: 46% improvement in disease-free survival in the tras arm (p<0.001); 50% improvement in recurrence-free survival (p<.001), and 49% decrease in distant recurrence (p<.001). They did not find a statistically significant improvement in overall survival. This study did not find an increase in cardiac toxicity, but further follow up is needed.
Results such as these certainly do not come along every day. As nurses, we need to understand the implications of such a trial and advocate for our patients. Even with more years of data to come, these trials have already begun to change the way that breast cancer is treated. If you have a chance, I highly recommend reading the original papers on these studies: Romond et al., NEJM ( Oct 20, 2005 )353:16 p. 1673 and Piccart-Gebhart et al., NEJM ( Oct 20, 2005 )353:16 p.1659.