One of four large, randomized trials to evaluate adjuvant trastuzumab (Herceptin) in early-stage HER2-positive breast cancer—and the only study to include a nonanthracycline chemotherapy regimen—found that regimen had similar efficacy to anthracycline-containing regimens, but with lower rates of cardiac dysfunction and leukemia.
The Breast Cancer International Research Group (BCIRG) 006 study compared doxorubicin and cyclophosphamide followed by docetaxel every 3 weeks (AC-T), to the same regimen plus 52 weeks of trastuzumab (AC-T plus trastuzumab), and to docetaxel and carboplatin plus 52 weeks of trastuzumab (TCH). The two regimens with trastuzumab were superior in efficacy to AC-T and had similar disease-free survival—84% among patients receiving AC-T plus trastuzumab and 81% among those receiving TCH—and overall survival—92% vs 91%.
“The risk–benefit ratio favored the nonanthracycline TCH regimen over AC-T plus trastuzumab, given its similar efficacy, fewer acute toxic effects, and lower risks of cardiotoxicity and leukemia,” the investigators stated in The New England Journal of Medicine.1
Protocol-specified Analysis
The 3,222 women participating in the study had HER2-positive, invasive, high-risk, node-negative or node-positive adenocarcinoma. Demographic and clinical characteristics, including cardiac risk factors, were similar among the women in the three treatment groups. At a median follow-up of 65 months, when 656 events triggered the protocol-specified analysis, the incidence of congestive heart failure was 2% in the group receiving AC-T plus trastuzumab, 0.7% in the AC-T group, and 0.4% in the TCH group.
“The incidence with AC-T plus trastuzumab as compared with TCH was increased by a factor of 5,” the authors reported. “The difference in rates of congestive heart failure between the two trastuzumab-containing regimens significantly favored TCH over AC-T plus trastuzumab (P < .001).” Seven cases of leukemia were reported in the groups receiving the anthracycline-based regimens. The one case in the TCH group occurred in a woman who had received an anthracycline for the treatment of a B-cell lymphoma after breast cancer was diagnosed.
“These observations establish TCH as another (but not ‘the’) standard of care for adjuvant treatment of HER2-positive early-stage breast cancer,” commented Daniel F. Hayes, MD, of the Breast Cancer Program, University of Michigan Comprehensive Cancer, Ann Arbor, in an editorial accompanying the study.2 He added that newer studies, some testing agents “that target HER2 in different ways or target complementary pathways,” could make for a brighter future for patients with HER2-positive breast cancer. ■
References
1. Slamon D, et al: Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 365:1273-1283, 2011.
2. Hayes DF: Steady progress against HER2-positive breast cancer. N Engl J Med 365:1336-1338, 2011.
