SAN ANTONIO—Interim analysis of a large trial of women treated with trastuzumab for human epidermal growth factor receptor type 2 (HER2)-positive breast cancer before or after surgery indicates that concurrent use with a taxane may improve overall survival (OS) and disease-free survival (DFS) compared with sequential administration. Previous trials have shown a large benefit of trastuzumab but left open the question of the optimal timing of its use. (See, eg, the HERA trial: Piccart-Gebhart MJ. N Engl J Med. 2005;353:1659-1672.)
At the San Antonio Breast Cancer Symposium in December 2009, Edith Perez, MD, director of the breast program at Mayo Clinic in Jacksonville, Florida, reported results of the N9831 trial that tested concurrent or sequential trastuzumab (San Antonio Breast Cancer Symposium; 2009. Abstract 80). The trial randomized women to one of three treatment arms: doxorubicin/cyclophosphamide then paclitaxel (control), doxorubicin/ cyclophospha mide, then paclitaxel, then trastuzumab for 52 weeks (sequential therapy), or doxorubicin/ cyclophosphamide, then paclitaxel plus trastuzumab for 12 weeks followed by trastuzumab for 40 weeks (concurrent therapy).
Compared with the control regimen (n = 1097), sequential therapy (n = 1087) was associated with a 30% benefit in DFS at a median of 5.5 years of followup (estimated hazard ratio [HR], 0.70; log rank P = .0005). An additional 23% benefit in DFS occurred in the concurrent therapy group (n = 949) when compared with the sequential arm at a median follow-up of 5.3 years (estimated HR, 0.77; log rank P = .019). Based on the specific statistical methods designed for interim analysis, however, this last difference was not deemed to be significant.
Perez presented results comparing control and concurrent therapy for a median follow-up of approximately 3 years. Compared with the control arm, concurrent therapy was associated with a 52% benefit in DFS (adjusted HR, 0.48; P < .00001) and a 35% benefit in OS (unadjusted HR, 0.65; P = .0007).
Speaking with The Oncology Pharmacist before her presentation, Perez said she thought the N9831 trial results would change practice patterns worldwide, especially in countries where the usual practice is sequential therapy. Most observers felt that the N9831 results made a good case for using concurrent trastuzumab with the taxane, although most said using sequential therapy would not be bad practice.
Julie Gralow, MD, professor of medical oncology at the University of Washington in Seattle, a coauthor of N9831, noted that the interim results involved less than one half of the planned events for which the study was powered to show a difference. She concluded that the results were still strong enough to recommend overlapping trastuzumab with a taxane.
Mark Pegram, MD, director of clinical research at the Sylvester Comprehensive Cancer Center of the University of Miami Miller School of Medicine in Florida, said, “While maybe not completely technically statistically significant…[the study is] so consistent with what was expected, based on all of the science, that I think it will be embraced fairly widely and fairly quickly.”
But Aman Buzdar, MD, of the M. D. Anderson Cancer Center in Houston, Texas, cautioned that physicians need to be familiar with using the drugs together and have to follow patients closely. “Some of the toxicities are also synergistic when you combine chemotherapeutic agents with antibody treatment,” he warned.