Adding trastuzumab (Herceptin) to adjuvant chemotherapy significantly improved disease-free survival of patients with resected stage I to III invasive HER2-positive breast cancer in the phase III North Central Cancer Treatment Group (NCCTG) N9831 trial. There was also a trend toward a further increase in disease-free survival when trastuzumab was administered concurrently rather than sequentially.
“On the basis of a positive risk-benefit ratio, we recommend that trastuzumab be incorporated into a concurrent regimen with taxane chemotherapy as an important standard-of-care treatment alternative to a sequential regimen,” the investigators stated in the Journal of Clinical Oncology.1
While other phase III clinical trials have assessed either sequential or concurrent incorporation of trastuzumab with chemotherapy, the NCCTG N9831 trial “is the only trial, to the best of our knowledge, prospectively comparing the two different approaches,” the researchers explained. “Specifically, it compares the efficacy and safety of chemotherapy alone (arm A), chemotherapy followed by sequential trastuzumab (arm B), and chemotherapy with concurrent trastuzumab followed by trastuzumab monotherapy (arm C).”
A comparison of arms A and B at a 6-year median follow-up showed “[Disease-free survival] was significantly increased with trastuzumab added sequentially to paclitaxel,” the authors reported. The 5-year disease-free survival rates were 71.8% in arm A, 80.1% in arm B, and 84.4% in arm C. “There was an increase in [disease-free survival] with concurrent trastuzumab and paclitaxel relative to sequential administration, … but the P value (.02) did not cross the prespecified O’Brien-Fleming boundary (.00116) for the interim analysis,” the authors stated. “Comparison of arm B and arm C with a median follow-up of 6 years indicates that although trastuzumab added sequentially to chemotherapy improves [disease-free survival], there is a strong trend toward a better outcome with concurrent trastuzumab,” they concluded.
Paclitaxel with trastuzumab after doxorubicin and cyclophosphamide “did not appear to have a significantly worse safety profile compared with sequential administration, including cardiac safety. ■
1. Perez EA, Romond EH, Suman VJ, et al: J Clin Oncol 29:3366-3373, 2011.
Seminal research in the treatment of HER2-positive breast cancer has been led by Edith A. Perez, MD, the Serene M. and Frances C. Durling Professor of Medicine at the Mayo Clinic, Jacksonville, Florida. The ASCO Post asked Dr. Perez to share her approach to HER2-directed therapy.