medication, clinically significant valvular heart disease,poorly controlled hypertension (diastolic > 100 mm Hg), any T4 or N2, or known N3 or M1 breast cancer werenot eligible.
Patients were randomized (1:1:1) to receive doxorubicin and cyclophosphamide followed by docetaxel (AC-T),doxorubicin and cyclophosphamide followed by docetaxel plus intravenous trastuzumab (AC-TH), or docetaxeland carboplatin plus intravenous trastuzumab (TCH). In both the AC-T and AC-TH arms, doxorubicin60 mg/m2 and cyclophosphamide 600 mg/m2 were administered every 3 weeks for four cycles; docetaxel100 mg/m2 was administered every 3 weeks for four cycles. In the TCH arm, docetaxel 75 mg/m2 andcarboplatin (at a target AUC of 6 mg/mL/min as a 30- to 60-minute infusion) were administered every 3 weeksfor six cycles. Intravenous trastuzumab was administered weekly (initial dose of 4 mg/kg followed by weeklydose of 2 mg/kg) concurrently with either T or TC, and then every 3 weeks (6 mg/kg) as monotherapy for a totalof 52 weeks. Radiation therapy, if administered, was initiated after completion of chemotherapy. Patients withER+ and/or PR+ tumors received hormonal therapy. DFS was the main outcome measure.
Among the 3222 patients randomized, the median age was 49 (range 22 to 74 years; 6% ≥ 65 years). Diseasecharacteristics included 54% ER+ and/or PR+ and 71% node positive. Prior to randomization, all patientsunderwent primary surgery for breast cancer.
The results for DFS for the integrated analysis of Studies NSABP B31 and NCCTG N9831, HERA, andBCIRG006 and OS results for the integrated analysis of Studies NSABP B31 and NCCTG N9831, and HERAare presented in Table 9. For Studies NSABP B31 and NCCTG N9831, the duration of DFS following a medianfollow-up of 2.0 years in the AC→TH arm is presented in Figure 1, and the duration of OS after a medianfollow-up of 8.3 years in the AC→TH arm is presented in Figure 2. The duration of DFS for BCIRG006 ispresented in Figure 3. Across all four studies, at the time of definitive DFS analysis, there were insufficientnumbers of patients within each of the following subgroups to determine if the treatment effect was differentfrom that of the overall patient population: patients with low tumor grade, patients within specific ethnic/racialsubgroups (Black, Hispanic, Asian/Pacific Islander patients), and patients>65 years of age. For Studies NSABPB31 and NCCTG N9831, the OS hazard ratio was 0.64 (95% CI: 0.55, 0.74). At 8.3 years of median follow-up[AC→TH], the survival rate was estimated to be 86.9% in the AC→TH arm and 79.4% in the AC→T arm. The
final OS analysis results from Studies NSABP B31 and NCCTG N9831 indicate that OS benefit by age,hormone receptor status, number of positive lymph nodes, tumor size and grade, and surgery/radiation therapywas consistent with the treatment effect in the overall population. In patients ≤ 50 years of age (n = 2197), the
OS hazard ratio was 0.65 (95% CI: 0.52, 0.81) and in patients > 50 years of age (n = 1866), the OS hazard ratiowas 0.63 (95% CI: 0.51, 0.78). In the subgroup of patients with hormone receptor-positive disease (ER-positive and/or PR-positive) (n = 2223), the hazard ratio for OS was 0.63 (95% CI: 0.51, 0.78). In the subgroup of
patients with hormone receptor-negative disease (ER-negative and PR-negative) (n = 1830), the hazard ratio forOS was 0.64 (95% CI: 0.52, 0.80). In the subgroup of patients with tumor size ≤ 2 cm (n = 1604), the hazardratio for OS was 0.52 (95% CI: 0.3 |
