Stage I, II, IIIA, and Operable IIIC Breast Cancer
Table 6. Standard Adjuvant Chemotherapy Regimens for Stage I, II, IIIA, and Operable IIICHER2/neuNon-Overexpressing Breast Cancer continued...
In the combined analysis of the NSABP-B-31 (NCT00004067) and Intergroup NCCTG-N9831 trials, trastuzumab was given weekly, concurrently, or immediately after the paclitaxel component of the AC with paclitaxel regimen.[Level of evidence: 1iiA] The results were confirmed in a joint analysis of the two studies, with a combined enrollment of 3,676 patients, that demonstrated a highly significant improvement in DFS (HR, 0.48; P < .001; 3-year DFS = 87% vs. 75%), as well as a significant improvement in OS (HR, 0.67; P = .015; 3-year OS = 94.3% vs. 91.7%; 4-year OS = 91.4% vs. 86.6%). Patients treated with trastuzumab experienced a longer DFS with a 52% lower risk of a DFS event (HR, 0.48; 95% CI, 0.39–0.59; P < .001), corresponding to an absolute difference in DFS of 11.8% at 3 years and 18% at 4 years. The risk of distant recurrence was 53% lower (HR, 0.47; 95%CI, 0.37–0.61; P < .001) in patients treated with trastuzumab, and the risk of death was 33% lower (HR, 0.67; 95%CI, 0.48–0.93; P = .015) in these patients.
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).