Tailored Dose-Dense Versus Standard Adjuvant Chemotherapy for High-Risk Early Breast Cancer: End-of-Study Results of the Randomized PANTHER Trial
Authors: Matikas Alexios , Möbus Volker , Greil Richard , Andersson Anne , Steger Günther G. , Untch Michael , Fornander Tommy , Malmström Per , Schmatloch Sabine , Johansson Hemming , Hellström Mats , Brandberg Yvonne , Gnant Michael , Loibl Sibylle , Foukakis Theodoros , Bergh Jonas ,   the SweBCG, ABCSG and GBG, Lohman Niklas , Söderberg Martin , Malmström Per , Einbeigi Zakaria , Karlsson Per , Linderholm Barbro , Holmberg Stig , Dabrosin Lotta , Hedayati Elham , Villman Kenneth , Rotstein Sam , Wallberg Birgitta , Fornander Tommy , Lindman Henrik , Ahlgren Johan , Edlund Per , Carlsson Lena , Bengtsson Nils-Olof , Karlsson Eva , Schmatloch Sabine , Kögel Matthias , Kohls Andreas , Grischke Eva-Maria , Baake Gerold , Hoffmann Gerald , Dietrich Maria , Möbus Volker , Adrion Ralf , Heyl Volker , Schnappauf Benjamin , Göhler Thomas , Ziemendorff Gabriele , Thalmann Ingo , Schumacher Claudia , Weiss Erich , Tomé Oliver , Bauer Wolfgang , Ober Angelika , Schneeweiss Andeas , Höffkes HG , Forstbauer Helmut , Solomayer Erich-Franz , Augustin Doris , Schultz Holger , Adhami Barmak , Niedermeier Michael , Ulmer Hans Ulrich , Hocke Andrea , Kusche Manfred , Hackenberg Reinhard , Rossmann Andreas , Lantzsch Tilmann , Schulze‐Tollert Jürgen , Lerchenmüller Christoph , Ladda Ekkehart , Wierick Elke , Tessen Hans Werner , Raudies Gerd , Sallmann Alexandra , Martin Berhardt , Uleer Christoph , Lübbe Kristina Maria , Felberbaum Ricardo , Wiest Wolfgang , Sütterlin Marc , Thomssen Christoph , Göhring Uwe-Jochen , Tesch Hans , Gatzweiler Axel , Janni Wolfgang , Schmidt Marcus , Werner Andeas , Bauer Lelia , Tulusan Agustinus , Park Tjong-Won , Berghorn Michael , Noesselt Thomas , Henschen Stephan , Stöger Herbert , Marth Christian , Pichler Angelika , Fridrik Michael , Ömer Volker , Lang Alois , Greil Richard , Weiß Harald , Andel Johannes , Thaler Josef , Galid Arik , Sevelda Paul , Singer Christian , Steger Günther , Melbinger‐Zeinitzer Elisabeth , Keckstein Jörg , Keil Felix , Tinchon Christoph , Kubista Ernst , Stierer Michael , Neumann Hans Jörg , Bauernhofer Thomas , Tschurtschenthaler Gertraud , Samonigg Hellmut 
Published: July 2024

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.