Author(s): Alexios Matikas, MD, PhD1,2; Volker Möbus, MD, PhD3; Richard Greil, MD, PhD4; Anne Andersson, MD, PhD5; Günther G. Steger, MD6; Michael Untch, MD, PhD7; Tommy Fornander, MD, PhD1; Per Malmström, MD, PhD8,9; Sabine Schmatloch, MD10; Mats Hellström, BSc2; Hemming Johansson, BSc1; Michael Gnant, MD, PhD11; Yvonne Brandberg, PhD1; Sibylle Loibl, MD, PhD12; Theodoros Foukakis, MD, PhD theodoros.foukakis@ki.se1,2; Jonas Bergh, MD, PhD1,2
ABSTRACT
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 JCO or elsewhere, for which the primary end point has already been reported.
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]; P = .030), event-free survival (HR, 0.78 [95% CI, 0.65 to 0.94]; P = .009), and distant disease-free survival (HR, 0.79 [95% CI, 0.64 to 0.98]; P = .030) while the improvement in overall survival was not statistically significant (HR, 0.82 [95% CI, 0.65 to 1.04]; P = .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.
Author Affiliations
1Oncology/Pathology Department, Karolinska Institutet, Stockholm, Sweden; 2Breast Center, Karolinska Comprehensive Cancer Center, Stockholm, Sweden; 3Department of Medicine II, Hematology & Oncology, University of Frankfurt, Frankfurt, Germany; 43rd Medical Department, Paracelsus Medical University and Salzburg Cancer Research Institute, Cancer Cluster Salzburg and AGMT, Salzburg, Austria; 5Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden; 6Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria; 7Helios Klinikum Berlin-Buch, Berlin, Germany; 8Division of Oncology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden; 9Department of Haematology, Oncology and Radiation Physics, Skåne University Hospital, Lund, Sweden; 10Elisabeth Hospital, Kassel, Germany; 11Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; 12German Breast Group, Neu-Isenburg, Germany
