Tailored Dose-Dense Versus Standard Adjuvant Chemotherapy for High-Risk Early Breast Cancer: End-of-Study Results of the Randomized PANTHER Trial
Alexios Matikas, Volker Möbus, Richard Greil, Anne Andersson, Günther Steger, Michael Untch, Tommy� Fornander, Per Malmström, Sabine Schmatloch, Hemming Johansson, Mats Hellström, Yvonne Brandberg, Michael Gnant, Sibylle Loibl, Theodoros Foukakis, Jonas Bergh, the SweBCG, ABCSG and GBG, Niklas Lohman, Martin Söderberg, Per Malmström, Zakaria Einbeigi, Per Karlsson, Barbro Linderholm, Stig Holmberg, Lotta Dabrosin, Elham Hedayati, Kenneth Villman, Sam Rotstein, Birgitta Wallberg, Tommy� Fornander, Henrik Lindman, Johan Ahlgren, Per Edlund, Lena Carlsson, Nils‐Olof Bengtsson, Eva Karlsson, Sabine Schmatloch, Matthias Kögel, A. Kohls, Eva‐Maria Grischke, Gerold Baake, G. W. Hoffmann, Maria Dietrich, Volker Möbus, Ralf Adrion, Volker Heyl, Benjamin Schnappauf, Thomas Göhler, Gabriele Ziemendorff, I. Thalmann, Claudia Schumacher, Erich Weiß, Oliver Tomé, Wolfgang Bauer, Angelika Ober, Andeas Schneeweiss, H.‐G. Höffkes, Helmut Forstbauer, Erich-Franz Solomayer, Doris Augustin, Holger Schultz, B Adhami, Michael Niedermeier, Hans Ulrich Ulmer, Andrea Hocke, M. Kusche, Reinhard Hackenberg, Andreas Roßmann, Tilmann Lantzsch, Jürgen Schulze‐Tollert, Christoph Lerchenmüller, Ekkehart Ladda, Elke Wierick, H.W. Tessen, Gerd Raudies, Alexandra Sallmann, Berhardt Martin, Christoph Uleer, Kristina Lübbe, R. Felberbaum, W. Wiest, Marc Sütterlin, Christoph Thomssen, Uwe-Jochen Göhring, Hans Tesch, Axel Gatzweiler, Wolfgang Janni, Marcus Schmidt, Andeas Werner, Lelia Bauer, Agustinus Tulusan, Tjong-Won Park, Michael Berghorn, Thomas Noesselt, Stephan Henschen, Herbert Stöger, Christian Marth, Angelika Pichler, Michael Fridrik, Volker Ömer
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.