ned final OS analysisfrom the joint analysis included 4063 patients and was performed when 707 deaths had occurred after a medianfollow-up of 8.3 years in the AC→paclitaxel + trastuzumab arm. The data from both arms in Study 1 and two ofthe three study arms in Study 2 were pooled for efficacy analyses. The patients included in the primary DFSanalysis had a median age of 49 years (range, 22 to 80 years; 6% > 65 years), 84% were white, 7% black,4% Hispanic, and 4% Asian/Pacific Islander. Disease characteristics included 90% infiltrating ductal histology,38% T1, 91% nodal involvement, 27% intermediate and 66% high grade pathology, and 53% ER+ and/orPR+ tumors. Similar demographic and baseline characteristics were reported for the efficacy eva luable
population, after 8.3 years of median follow-up in the AC→paclitaxel + trastuzumab arm.Study 3
In Study 3, breast tumor specimens were required to show HER2 overexpression (3+ by IHC) or geneamplification (by FISH) as determined at a central laboratory. Patients with node-negative disease wererequired to have ≥ T1c primary tumor. Patients with a history of congestive heart failure or LVEF < 55%,uncontrolled arrhythmias, angina requiring medication, clinically significant valvular heart disease, evidence oftransmural infarction on ECG, poorly controlled hypertension (systolic > 180 mm Hg ordiastolic > 100 mm Hg) were not eligible.
Study 3 was designed to compare one and two years of three-weekly trastuzumab treatment versus observationin patients with HER2 positive EBC following surgery, established chemotherapy and radiotherapy (ifapplicable). Patients were randomized (1:1:1) upon completion of definitive surgery, and at least four cycles of
chemotherapy to receive no additional treatment, or one year of trastuzumab treatment or two years oftrastuzumab treatment. Patients undergoing a lumpectomy had also completed standard radiotherapy. Patientswith ER+ and/or PgR+ disease received systemic adjuvant hormonal therapy at investigator discretion.
Trastuzumab was administered with an initial dose of 8 mg/kg followed by subsequent doses of 6 mg/kg onceevery three weeks. The main outcome measure was Disease-Free Survival (DFS), defined as in Studies 1 and 2.
A protocol-specified interim efficacy analysis comparing one-year trastuzumab treatment to observation wasperformed at a median follow-up duration of 12.6 months in the trastuzumab arm and formed the basis for thedefinitive DFS results from this study. Among the 3386 patients randomized to the observation (n = 1693) and
trastuzumab one-year (n = 1693) treatment arms, the median age was 49 years (range 21 to 80), 83% wereCaucasian, and 13% were Asian. Disease characteristics: 94% infiltrating ductal carcinoma, 50% ER+ and/orPgR+, 57% node positive, 32% node negative, and in 11% of patients, nodal status was not assessable due to
prior neo-adjuvant chemotherapy. Ninety-six percent (1055/1098) of patients with node-negative disease hadhigh-risk features: among the 1098 patients with node-negative disease, 49% (543) were ER and PgR, and 47% (512) were ER and/or PgR + and had at least one of the following high-risk features: pathological tumorsize greater than 2 cm, Grade 2 to 3, or age < 35 years. Prior to randomization, 94% of patients had receivedanthracycline-based chemotherapy regimens.
After the definitive DFS results comparing observation to one-year trastuzumab treatment were disclosed, aprospecti |
