Long-Term Follow-Up of E1199 Trial Shows Maintained Benefit of Adjuvant Weekly Paclitaxel in Breast Cancer, Particularly Triple-Negative Disease
In long-term follow-up of the phase III E1199 trial reported in the Journal of Clinical Oncology by Sparano et al, adjuvant weekly paclitaxel and every-3-week docetaxel were associated with significantly longer disease-free survival and numerically longer overall survival vs every-3-week paclitaxel in women with stage II or III breast cancer. A pronounced effect of weekly paclitaxel was observed in women with triple-negative disease.
Disease-Free and Overall Survival
In E1199, 4,954 women were randomly assigned in 2×2 factorial design to four cycles of doxorubicin-cyclophosphamide plus paclitaxel or docetaxel every 3 weeks for 4 doses or weekly for 12 doses.
Median follow-up in the current report was 12.1 years. As in the original report from the trial, there was no significant difference in overall survival or disease-free survival between the paclitaxel groups and the docetaxel groups or between schedules within the paclitaxel and docetaxel groups. The taxane-by-schedule interaction remained significant for disease-free survival (hazard ratio [HR] = 1.46, P < .001) and overall survival (HR = 1.36, P = .007), indicating that weekly paclitaxel and every-3-week docetaxel were superior to every-3-week paclitaxel.
Compared with every-3-week paclitaxel, disease-free survival was significantly improved and overall survival was numerically improved with weekly paclitaxel (HR = 0.84, P = .011, and HR = 0.87, P = .09) and every-3-week docetaxel (HR = 0.79, P = .001, and HR = 0.86, P = .054).
Subgroups
Among 1,025 women with triple-negative disease, weekly paclitaxel was associated with significantly improved disease-free survival (HR = 0.69, P = .010) and overall survival (HR = 0.69, P = .019) vs every-3-week paclitaxel, with no significant benefit observed with docetaxel via either schedule. Among 2,879 patients with hormone receptor–positive and HER2-negative/unknown disease, every-3-week docetaxel was associated with improved disease-free survival (HR = 0.76, P = .004) but not overall survival vs every-3-week paclitaxel, with no differences observed for weekly paclitaxel or docetaxel. No differences among groups were observed among 971 patients with HER2-positive disease.
In multivariate analysis, among patients with hormone receptor–positive/HER2-negative/unknown disease, obesity was associated with significantly poorer disease-free survival (HR = 1.24, P = .003) and overall survival (HR = 1.29, P = .002) in nonblack patients. Black race was associated with significantly poorer disease-free (HR = 2.29, P < .001) and overall survival (HR = 2.24, P < .001) vs nonblack race in nonobese patients but not in obese patients.
The investigators concluded: “Improved outcomes initially observed for weekly paclitaxel were qualitatively similar but quantitatively less pronounced with longer follow-up, although exploratory analysis suggested substantial benefit in triple-negative disease. Further research is required to understand why obesity and race influence clinical outcome in hormone receptor–positive disease.”
Joseph A. Sparano, MD, of Albert Einstein College of Medicine, is the corresponding author of the Journal of Clinical Oncology article.
The study was supported by grants from the National Cancer Institute. For full disclosures of the study authors, visit jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
