Long-Term follow-up of S0221, comparing alternative Dose-Schedules of anthracycline/taxane therapy in early breast cancer

Background S0221 investigated weekly vs (vs) every 2 weeks (Q2W) dosing of doxorubicin(A)/cyclophosphamide (C) followed by paclitaxel (P) in patients with high-risk early breast cancer. After an interim analysis, randomization to the two AC arms was stopped for futility and the trial was modified to study only the P schedules. Patients and Methods Between December 2003 and November 2010, 2716 patients were randomized in a 2 x 2 factorial design to: 15 weeks of weekly A and daily C vs 6 cycles of Q2W AC; and weekly P for 12 weeks vs 6 cycles of Q2W P. Between January 2011 and January 2012, an additional 578 patients were assigned to 4 cycles of Q2W AC x 4 and randomized to weekly vs Q2W P. Updated survival was assessed using log-rank tests and Cox regression models. We compared outcomes by breast cancer subtype as well. Results At a median follow-up of 12.1 years, there were no significant differences among the four treatment arms in disease free survival [DFS] (p = 0.91) or overall survival [OS] (p = 0.34) in the original protocol. Among the 578 patients assigned AC for 4 cycles and randomized to P weekly vs Q2W P, there were no overall differences in DFS (p = 0.32) or OS (p = 0.42). Conclusion As there were no significant outcome differences in DFS or OS between the studied schedules of AC and P with extended follow-up in the original or revised protocol, either paclitaxel schedule may be recommended, with selection based on toxicity, cost, or patient preference.