As reported in the Journal of Clinical Oncology by Matikas et al, the prespecified end-of-study analysis of the European phase III PANTHER trial showed significant improvements in outcomes with tailored dose-dense vs standard adjuvant chemotherapy in patients with high-risk early breast cancer.
As stated by the investigators, “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…compared sequential epirubicin/cyclophosphamide and docetaxel administered either once every 2 [weeks] or once every 3 weeks, with tailored dosing at the dose-dense schedule according to hematologic toxicity.”
Study Details
In the trial, 2,003 patients from sites in Austria, Germany, and Sweden were randomly assigned to tailored dose-dense (n = 1,001) or standard-interval (n = 1,002) adjuvant chemotherapy.
Tailored dose-dense therapy consisted of epirubicin and cyclophosphamide every 2 weeks for four cycles followed by four cycles of docetaxel every 2 weeks, with dose tailoring for each cycle decided according to a predefined toxicity algorithm. Patients in the standard group received three cycles of fluorouracil and epirubicin and cyclophosphamide every 3 weeks followed by three cycles of docetaxel every 3 weeks.
The primary analysis of the trial, reported after a median follow-up of 5.3 years, showed that primary and secondary time-to-event outcomes favored the tailored dose-dense group, although a significant difference was observed only for event-free survival.
The end-of-study analysis presents findings after a median of 10.3 years of follow-up.
Key Findings
Compared with standard adjuvant chemotherapy, tailored dose-dense treatment was associated with significantly improved breast cancer recurrence-free survival (hazard ratio [HR] = 0.80, 95% confidence interval [CI] = 0.65–0.98, P = .030), event-free survival (HR = 0.78, 95% CI = 0.65–0.94, P = .009), and distant disease–free survival (HR = 0.79, 95% CI = 0.64–0.98, P = .030). A numeric improvement in overall survival did not achieve statistical significance (HR = 0.82, 95% CI = 0.65–1.04, P = .109).
The investigators concluded, “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.”
Theodoros Foukakis, MD, PhD, of the Oncology/Pathology Department, Karolinska Institutet, Stockholm, Sweden, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Swedish Cancer Society, Swedish Breast Cancer Association, Amgen, Roche, Sanofi-Aventis, and others. For full disclosures of the study authors, visit ascopubs.org.
