were Asian. Disease characteristics: 94% infiltrating ductal carcinoma, 50%ER+ and/or PgR+, 57% node positive, 32% node negative, and in 11% of patients, nodal status was notassessable due to prior neo-adjuvant chemotherapy. Ninety-six percent (1055/1098) of patients withnode-negative disease had high 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 followinghigh risk features: pathological tumor size greater than 2 cm, Grade 2–3, or age < 35 years. Prior torandomization, 94% of patients had received anthracycline-based chemotherapy regimens.
After the definitive DFS results comparing observation to one-year trastuzumab treatment were disclosed,a prospectively planned analysis that included comparison of one year versus two years of trastuzumabtreatment at a median follow-up duration of 8 years was performed. Based on this analysis, extendingtrastuzumab treatment for a duration of two years did not show additional benefit over treatment for oneyear [Hazard Ratios of two-years trastuzumab versus one-year trastuzumab treatment in the intent to treat(ITT) population for Disease-Free Survival (DFS) = 0.99 (95% CI: 0.87, 1.13), p-value = 0.90 and OverallSurvival (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, ornode-negative disease 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, myocardialinfarction, Grade 3 or 4 cardiac arrhythmia, angina requiring medication, clinically significant valvular heartdisease, poorly controlled hypertension (diastolic > 100 mm Hg), any T4 or N2 or known N3 or M1 breastcancer 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 docetaxeland carboplatin plus trastuzumab (TCH). In both the AC-T and AC-TH arms, doxorubicin 60 mg/m2
and
cyclophosphamide 600 mg/m2
were administered every 3 weeks for four cycles; docetaxel 100 mg/m2
was
administered every 3 weeks for four cycles. In the TCH arm, docetaxel 75 mg/m2and 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 ERand/or PR+ tumors received hormonal therapy. Disease-Free Survival (DFS) was the main outcomemeasure.
Among the 3222 patients randomized, the median age was 49 (range 22 to 74 years; 6% ≥ 65 years).
Disease characteristics included 54% ER+ and/or PR+ and 71% node positive. Prior to randomization, allpatients underwent 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 forthe integrated analysis of Studies 1 and 2, and Study 3 are presented in Table 9. For Studies 1 |
