Author(s): Sanne A.L. Bartels, MD, PhD, MSc1,2; Mila Donker, MD, PhD2,3; Coralie Poncet, MSc1; Nicolas Sauvé, MSc1; Marieke E. Straver, MD, PhD4; Cornelis J.H. van de Velde, MD, PhD5; Robert E. Mansel, MD, MS6; Charlotte Blanken, MD, PhD7; Lorenzo Orzalesi, MD, PhD8; Jean H.G. Klinkenbijl, MD, PhD9; Huub C.J. van der Mijle, MD, PhD10; Grard A.P. Nieuwenhuijzen, MD, PhD11; Sanne C. Veltkamp, MD, PhD12; Thijs van Dalen, MD, PhD13; Andreas Marinelli, MD, PhD4; Herman Rijna, MD, PhD14; Marko Snoj, MD, PhD15; Nigel J. Bundred, MD, PhD16; Jos W.S. Merkus, MD, PhD17; Yazid Belkacemi, MD, PhD18,19; Patrick Petignat, MD20; Dominic A.X. Schinagl, MD, PhD21; Corneel Coens, MSc1; Geertjan van Tienhoven, MD, PhD22; Frederieke van Duijnhoven, MD, PhD2; and Emiel J.T. Rutgers, MD, PhD2
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.
The European Organisation for Research and Treatment of Cancer 10981-22023 AMAROS trial evaluated axillary lymph node dissection (ALND) versus axillary radiotherapy (ART) in patients with cT1-2, node-negative breast cancer and a positive sentinel node (SN) biopsy. At 5 years, both modalities showed excellent and comparable axillary control, with significantly less morbidity after ART. We now report the preplanned 10-year analysis of the axillary recurrence rate (ARR), overall survival (OS), and disease-free survival (DFS), and an updated 5-year analysis of morbidity and quality of life.
In this open-label multicenter phase III noninferiority trial, 4,806 patients underwent SN biopsy; 1,425 were node-positive and randomly assigned to either ALND (n = 744) or ART (n = 681).
Per intention-to-treat analysis, 10-year ARR cumulative incidence was 0.93% (95% CI, 0.18 to 1.68; seven events) after ALND and 1.82% (95% CI, 0.74 to 2.94; 11 events) after ART (hazard ratio [HR], 1.71; 95% CI, 0.67 to 4.39). There were no differences in OS (HR, 1.17; 95% CI, 0.89 to 1.52) or DFS (HR, 1.19; 95% CI, 0.97 to 1.46). ALND was associated with a higher lymphedema rate in updated 5-year analyses (24.5% v 11.9%; P < .001). Quality-of-life scales did not differ by treatment through 5 years. Exploratory analysis showed a 10-year cumulative incidence of second primary cancers of 12.1% (95% CI, 9.6 to 14.9) after ART and 8.3% (95% CI, 6.3 to 10.7) after ALND.
This 10-year analysis confirms a low ARR after both ART and ALND with no difference in OS, DFS, and locoregional control. Considering less arm morbidity, ART is preferred over ALND for patients with SN-positive cT1-2 breast cancer.
Author Affiliations1European Organisation for Research and Treatment of Cancer Headquarters, Brussels, Belgium; 2Department of Surgical Oncology, the Netherlands Cancer Institute, Amsterdam, the Netherlands; 3Department of Radiation Oncology, Leiden University Medical Center, Leiden, the Netherlands; 4Department of Surgery, Haaglanden Medical Center, Den Haag, the Netherlands; 5Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands; 6Department of Surgery, Cardiff University, Cardiff, United Kingdom; 7Department of Surgery, Rijnstate Hospital, Arnhem, the Netherlands; 8Breast Unit, Careggi University Hospital, Florence, Italy; 9Department of Surgery, Gelre Hospital, Apeldoorn, the Netherlands; 10Department of Surgery, Nij Smellinghe Hospital, Drachten, the Netherlands; 11Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands; 12Department of Surgery, Amstelland Hospital, Amstelveen, the Netherlands; 13Department of Surgery, Diakonessenhuis, Utrecht, the Netherlands; 14Department of Surgery, Spaarne Gasthuis, Haarlem, the Netherlands; 15Department of Surgery, Institute of Oncology, Ljubljana, Slovenia; 16Department of Surgery, University of Manchester and Manchester University Foundation Trust, Manchester, United Kingdom; 17Department of Surgery, Haga Hospital, Den Haag, the Netherlands; 18Department of Radiation Oncology, Centre Oscar Lambret, Lille, France; 19AP-HP, Radiation Therapy and Breast Center of Henri Mondor, University of Paris Est Creteil (UPEC), Créteil, France; 20Division of Gynecology, Geneva University Hospital, Geneva, Switzerland; 21Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, the Netherlands; 22Department of Radiation Oncology, Cancer Center Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands