The first analysis of SWOG S0221,7,8 a phase 3 trial that compared adjuvant doxorubicin, cyclophosphamide, and paclitaxel in patients with high-risk early breast cancer, reported at the 2011 American Society of Clinical Oncology Annual Meeting that the study’s data and safety monitoring committee recommended stopping randomization to the doxorubicin, cyclophosphamide, and filgrastim arm due to futility. The trial reopened and randomized patients to two paclitaxel arms after 4 cycles of doxorubicin, cyclophosphamide, and pegfilgrastim. The final data collection date for the primary outcome measure is expected February 2017.8

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In the phase 3 randomized GEICAM/2003-02 trial reported at ASCO 2012,1,2 patients 18-70 years of age with T1-T3/N0 operable breast cancer and at least one high-risk St. Gallen 1998 criteria (defined as size >2 cm, hormone-receptor negative, grade 2/3, age <35 years), adequate cardiac function (normal LVEF was required), and adequate liver, renal, and bone marrow function were eligible to enroll.

Although patients whose tumors were HER2+ were initially allowed, after 792 had entered the trial, the study was amended in 2006 to exclude them. Patients were stratified by site, menopausal status, nodal status diagnostic method (sentinel-node biopsy vs lymphadenectomy), and hormone receptor status and randomly assigned to 6 cycles of FAC (500/50/500mg/m2 every 3 weeks) or 4 cycles of FAC followed by weekly paclitaxel (100mg/m2 weekly) for 8 cycles.

Primary study end point was DFS. The trial was designed to detect an absolute 5-year increase in DFS of 5% (80% FAC, 85% FAC followed by weekly paclitaxel). To detect this difference, a sample size of 1,812 evaluable patients were required, 906 per arm; however, assuming a drop-out rate of 6%, 1,929 patients were required. First analysis of DFS was planned when a median follow-up of 5 years was reached and final analysis is triggered by 316 events.

Secondary outcomes are overall survival (OS), toxicity, quality of life, and predictive biomarkers of efficacy of paclitaxel.

Between September 2003 and October 2008, 1,925 patients were randomized, 975 to the FAC arm and 951 to the FAC plus weekly paclitaxel arm. Baseline characteristics were well balanced between the two arms. Median age was 50 years, 73% of patients were hormone-receptor positive, and 10% were HER2+. A total of 97% of patients in the FAC arm and 85% of those in the FAC followed by weekly paclitaxel arm completed all treatment as planned, Dr. Martin reported. Median dose intensity was 98% with 6 cycles of FAC, 99% with 4 cycles of FAC, and 98% with weekly paclitaxel.

The most frequent grade 3/4 hematologic toxicities (>1% in either arm) with FAC vs FAC followed by weekly paclitaxel were neutropenia (25.4% vs 21.8%; P=0.05918), febrile neutropenia (3.6% vs 2.75%; P=0.28566), lymphopenia (1.03% vs 0.85%; P=0.67589), leukopenia (9.37% vs 8.46%; P=0.48219), and infection (0.62% vs 2.54%; P=0.00071).