Tailored Dose-Dense Versus Standard Adjuvant Chemotherapy for High-Risk Early Breast Cancer: End-of-Study Results of the Randomized PANTHER Trial.

Abstract

<i>Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in</i> JCO <i>or elsewhere, for which the primary end point has already been reported</i>.Although dose-dense adjuvant chemotherapy administered once every 2 weeks leads to superior outcomes compared with standard regimens once every 3 weeks, the observed improvement is largely limited to studies using the suboptimal paclitaxel schedule once every 3 weeks as control. PANTHER is an international phase III trial which compared sequential epirubicin/cyclophosphamide and docetaxel administered either once every 2 or once every 3 weeks, with tailored dosing at the dose-dense schedule according to hematologic toxicity. In this end-of-study analysis, the median follow-up was 10.3 years. Compared with standard adjuvant chemotherapy, dose-dense treatment improved breast cancer recurrence-free survival (hazard ratio [HR], 0.80 [95% CI, 0.65 to 0.98]; <i>P</i> = .030), event-free survival (HR, 0.78 [95% CI, 0.65 to 0.94]; <i>P</i> = .009), and distant disease-free survival (HR, 0.79 [95% CI, 0.64 to 0.98]; <i>P</i> = .030) while the improvement in overall survival was not statistically significant (HR, 0.82 [95% CI, 0.65 to 1.04]; <i>P</i> = .109). To our knowledge, this is the first trial that confirms the benefit of a dose-dense regimen over a control regimen containing docetaxel once every 3 weeks.