111MO Tailored dose-dense versus standard adjuvant chemotherapy for high-risk early breast cancer: Efficacy outcomes and key subgroups after 10 years of follow-up in the randomized phase III PANTHER trial

An individual patient-level meta-analysis has shown that dose dense adjuvant chemotherapy administered every two weeks leads to superior outcomes compared to standard regimens every three weeks. However, most studies used the suboptimal three-weekly paclitaxel as control and were carried out before the introduction of adjuvant trastuzumab and extended endocrine therapy. PANTHER is an international, randomized phase III trial which compared 4 cycles of leukocyte nadir-based tailored and dose-dense adjuvant epirubicin and cyclophosphamide every 2 weeks followed by 4 cycles of tailored dose-dense docetaxel every 2 weeks (tDD EC/D), or to standard-interval chemotherapy with 3 cycles of fluorouracil and epirubicin-cyclophosphamide every 3 weeks followed by 3 cycles of docetaxel every 3 weeks. The primary end point was breast cancer recurrence-free survival (BCRFS). The primary analysis at 5 years (Foukakis et al JAMA 2016) demonstrated an improvement of event-free survival with dose-dense therapy but no significant difference in BCRFS. Between February 2007 and September 2011, 2017 patients were enrolled in the trial and 2003 patients comprise the intention-to-treat population. After a median follow-up of 10.3 years (interquartile range, 9.1 – 10.5 years), there were 179 breast cancer relapses in the experimental and 218 in the control group. Treatment with tDD EC/D improved the primary endpoint of BCRFS (HR=0.80, 95% CI 0.65 – 0.98, p=0.030; 10-year event rate 18.6% vs 22.3%, absolute difference 3.7% ± 1.9%). The improvement in BCRFS was noted across subgroups according to hormone receptor and HER2 expression, anatomic stage, and other demographic and pathologic factors. The difference in overall survival was not statistically significant (HR=0.82, 95% CI 0.65 – 1.04, p=0.109; 10-year event rate 15.1% vs 16.6%, absolute difference 1.5% ± 1.7%). After 10 years of follow-up in the PANTHER trial, tailored dose-dense adjuvant chemotherapy improved BCRFS compared with standard adjuvant chemotherapy containing 3-weekly docetaxel.