vely planned analysis that included comparison of one year versus two years of trastuzumab treatmentat a median follow-up duration of 8 years was performed. Based on this analysis, extending trastuzumab
treatment for a duration of two years did not show additional benefit over treatment for one year [Hazard Ratiosof two-years trastuzumab versus one-year trastuzumab treatment in the intent to treat (ITT) population forDisease-Free Survival (DFS) = 0.99 (95% CI: 0.87, 1.13), p-value = 0.90 and Overall Survival (OS) = 0.98
(0.83, 1.15); p-value = 0.78].
Study 4
In Study 4, breast tumor specimens were required to show HER2 gene amplification (FISH+ only) asdetermined at a central laboratory. Patients were required to have either node-positive disease, or node-negativedisease with at least one of the following high-risk features: ER/PR-negative, tumor size > 2 cm, age < 35 years,
or histologic and/or nuclear Grade 2 or 3. Patients with a history of CHF, myocardial infarction, Grade 3 or 4cardiac arrhythmia, angina requiring medication, clinically significant valvular heart disease, poorly controlledhypertension (diastolic > 100 mm Hg), any T4 or N2 or known N3 or M1 breast cancer were not eligible.
Patients were randomized (1:1:1) to receive doxorubicin and cyclophosphamide followed by docetaxel (AC-T),doxorubicin and cyclophosphamide followed by docetaxel plus trastuzumab (AC-TH), or docetaxel andcarboplatin plus trastuzumab (TCH). In both the AC-T and AC-TH arms, doxorubicin 60 mg/m2 andcyclophosphamide 600 mg/m2 were administered every 3 weeks for four cycles; docetaxel 100 mg/m2 wasadministered every 3 weeks for four cycles. In the TCH arm, docetaxel 75 mg/m2 and carboplatin (at a targetAUC of 6 mg/mL/min as a 30- to 60-minute infusion) were administered every 3 weeks for six cycles.
Trastuzumab was administered weekly (initial dose of 4 mg/kg followed by weekly dose of 2 mg/kg)concurrently with either T or TC, and then every 3 weeks (6 mg/kg) as monotherapy for a total of 52 weeks.
Radiation therapy, if administered, was initiated after completion of chemotherapy. Patients with ER+ and/orPR+ tumors received hormonal therapy. Disease-Free Survival (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 1 and 2, Study 3, and Study 4 and OS results for theintegrated analysis of Studies 1 and 2, and Study 3 are presented in Table 9. For Studies 1 and 2, the duration ofDFS following a median follow-up of 2.0 years in the AC→TH arm is presented in Figure 4, and the duration of
OS after a median follow-up of 8.3 years in the AC→TH arm is presented in Figure 5. The duration of DFS forStudy 4 is presented in Figure 6. Across all four studies, at the time of definitive DFS analysis, there wereinsufficient numbers of patients within each of the following subgroups to determine if the treatment effect was
different from that of the overall patient population: patients with low tumor grade, patients within specificethnic/racial subgroups (Black, Hispanic, Asian/Pacific Islander patients), and patients > 65 years of age. ForStudies 1 and 2, the OS hazard ratio was 0.64 (95% CI: 0.55, 0.74). At 8.3 years of median follow-up
[AC→TH], the surviva |
