SAN ANTONIOA second interim efficacy analysis of the phase III Breast Cancer International Research Group (BCIRG) 006 study confirmed the benefits reported previously for docetaxel(Drug information on docetaxel) (Taxotere)-plus-trastuzumab (Herceptin) regimens in early HER2-positive breast cancer, and further showed a higher rate of toxicity for anthracycline-based regimens. The updated findings, in fact, raise the provocative question of whether, in some patients, anthracyclines do more harm than good. Dennis Slamon, MD, PhD, co-chair of the study and director of Clinical and Translational Research at UCLA's Jonsson Comprehensive Cancer Center, reported the results at the 29th Annual San Antonio Breast Cancer Symposium (abstract 52).
BCIRG 006 randomized 3,222 women with primary HER2-positive and either node-positive or high-risk node-negative breast cancer to one of three regimens: a control arm of four cycles of doxorubicin(Drug information on doxorubicin) and cyclophosphamide(Drug information on cyclophosphamide) followed by four cycles of docetaxel (AC-T); an experimental arm of the AC-T regimen followed by one year of trastuzumab (AC-TH); and an experimental arm of docetaxel, carboplatin(Drug information on carboplatin), and one year of trastuzumab(Drug information on trastuzumab) (TCH).
Median follow-up was 23 months at the first analysis, reported at ASCO 2005, and is now 36 months. The current analysis is based on 462 disease-free survival events (up from 322 in the ASCO 2005 report) and 185 deaths (up from 84).
The number of observed events at the second analysis was significantly greater with AC-T (192) vs AC-TH (128) (P = .000011) or TCH (142) (P = .00028). By contrast, the number of observed events was comparable between AC-TH and TCH (P = .42).
Compared with AC-T, the relative reduction in the risk of relapse was 39% with AC-TH (P < .0001) and 33% with TCH (P = .0003). The absolute difference in disease-free survival (DFS) was similar for the arms containing trastuzumab (6% with AC-TH and 5% with TCH). Notably, node-negative patients (29% of the population) derived this magnitude of benefit as well. Metastatic events were reported for 143 patients with AC-T (13.1%) vs 93 with AC-TH (8.7%) and 98 (9.1%) with TCH.The relative reduction in risk of death was 41% (P < .0041) and 34% (P < .017), respectively, for AC-TH and TCH vs the control arm. At 4 years, 92% and 91% of patients were alive in the AC-TH and TCH arms, respectively, vs 86% in the AC-T arm. For all subpopulations, disease-free and overall survival were improved with AC-TH and TCH vs AC-T.
Differences in Safety Profile
The cardiotoxicity of the two experimental arms significantly favored the nonanthracycline TCH regimen. Grade 3-4 cardiac left ventricular failure (congestive heart failure) occurred in only 4 TCH patients vs 20 AC-TH patients (P = .0015). There were 50% fewer cases of patients with greater than 10% relative LVEF decline in the TCH arm (8.5%), compared with AC-TH (18%) (P < .0001).