Table 6. Standard Adjuvant Chemotherapy Regimens for Stage I, II, IIIA, and Operable IIICHER2/neuNon-Overexpressing Breast Cancer continued...
In the BCIRG-006 (NCT00021255) trial, 3,222 women with early stage HER2-overexpressing breast cancer were randomly assigned to receive AC followed by docetaxel (AC-T) versus AC followed by docetaxel plus trastuzumab (AC-T plus trastuzumab) versus docetaxel, carboplatin, plus trastuzumab (TCH, a nonanthracycline-containing regimen).[Level of Evidence: 1iiA] A significant benefit with respect to DFS and OS was seen in both groups treated with trastuzumab-containing regimens compared with the control group that did not receive trastuzumab. The control group had a 5-year DFS rate of 75% and an OS rate of 87%. For patients receiving AC-T plus trastuzumab, the 5-year DFS rate was 84% (HR for the comparison with AC-T = 0.64; P < .001), and the OS rate was 92% (HR, 0.63; P < .001). For patients receiving TCH, the 5-year DFS rate was 81% (HR, 0.75; P = .04), and the OS rate was 91% (HR, 0.77; P = .04).
The authors stated that there was no significant difference in DFS or OS between the two trastuzumab-containing regimens. However, the study was not powered to detect equivalence between the two trastuzumab-containing regimens. The rates of congestive heart failure and cardiac dysfunction were significantly higher in the group receiving AC-T plus trastuzumab than in the docetaxel and carboplatin plus 52 weeks of trastuzumab (TCH) group (P < .001). These trial findings raise the question of whether anthracyclines are needed for the adjuvant treatment of HER2-overexpressing breast cancer. The group receiving AC-trastuzumab showed a small but not statistically significant benefit over TCH. This trial supports the use of TCH as an alternative adjuvant regimen for women with early-stage HER2-overexpressing breast cancer, particularly in those with concerns about cardiac toxic effects.
The AVENTIS-TAX-GMA-302 study was a three-arm large trial containing two anthracycline arms (AC-D: doxorubicin, cyclophosphamide, docetaxel or AC-DH: doxorubicin, cyclophosphamide, docetaxel, and trastuzumab) and a nonanthracycline one (DCbH: docetaxel, carboplatin, trastuzumab). In its second interim efficacy analysis with a median follow-up of 36 months, there were 462 DFS events and 185 deaths. For DFS, the HR was 0.61 for patients in the AC-DH arm (95% CI, 0.48–0.76; P < .001) and 0.67 for patients in the DCbH arm (95% CI, 0.54–0.83; P = .003), compared with the AC-D. This translated to absolute benefits (from years 2 to 4) of 6% and 5%, respectively with the addition of trastuzumab. Nevertheless, longer follow-up is needed in patients in the DCbH arm to warrant the omission of anthracyclines in these patients.
The Finland Herceptin (FINHER) study assessed the impact of a much shorter course of trastuzumab. In this trial, 232 women younger than 67 years with node-positive or high-risk (>2 cm tumor size) node-negative HER2-overexpressing breast cancer were given nine weekly infusions of trastuzumab concurrently with docetaxel or vinorelbine followed by FEC. At a 3-year median follow-up, the risk of recurrence and/or death was significantly reduced in patients receiving trastuzumab (HR, 0.41; P = .01; 95% CI, 0.21–0.83; 3 year DFS = 89% vs. 78%). The difference in OS (HR, 0.41) was not statistically significant (P = .07; 95% CI, 0.16–1.08).[Level of evidence: 1iiA]