Table 6. Standard Adjuvant Chemotherapy Regimens for Stage I, II, IIIA, and Operable IIICHER2/neuNon-Overexpressing Breast Cancer continued...
Several phase III, clinical trials have addressed the role of the anti-HER2/neu antibody, trastuzumab, as adjuvant therapy for patients with HER2-overexpressing cancers.
In the HERceptin Adjuvant (HERA) (BIG-01-01 [NCT00045032]) trial, which is the largest study (5,090 patients), trastuzumab was given every 3 weeks within 7 weeks of the completion of primary therapy that included an anthracycline-containing chemotherapy regimen given preoperatively or postoperatively plus or minus locoregional radiation therapy.[Level of evidence: 1iiA] Although the results of the comparison of 1 year versus 2 years of trastuzumab have not been released yet, there are available data for 3,387 patients (1,694 in the 1-year trastuzumab arm and 1,693 in the observation arm). Of these patients, the median age was 49 years, about 33% had node-negative disease, and nearly 50% had hormone receptor (ER and PR)-negative disease. Patients who were treated with 1 year of trastuzumab experienced a 46% lower risk of a first event (hazard ratio [HR], 0.54; 95% CI, 0.43–0.67; P < .001), corresponding to an absolute DFS benefit of 8.4% at 2 years (95% CI, 2.1–14.8). The updated results at 23.5 months' follow-up showed an unadjusted HR for the risk of death with trastuzumab compared with observation of 0.66 (95% CI, 0.47–0.91; P = .0115), corresponding to an absolute OS benefit of 2.7%. There were 218 DFS events reported with trastuzumab compared with 321 DFS events reported with observation. The unadjusted HR for the risk of an event with trastuzumab was 0.64 (0.54–0.76; P < .001), corresponding to an absolute DFS benefit of 6.3%.
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.