Ulrike A Nitz1,2, Oleg Gluz1,2,3, Sherko Kümmel1,4,5, Matthias Christgen6, Michael Braun7, Bahriye Aktas8,9, Kerstin Lüdtke-Heckenkamp10, Helmut Forstbauer11, Eva-Maria Grischke12, Claudia Schumacher13, Maren Darsow14, Katja Krauss15, Benno Nuding16, Marc Thill17, Jochem Potenberg18, Christoph Uleer19, Mathias Warm20, Hans Holger Fischer21, Wolfram Malter3, Michael Hauptmann22,23, Ronald E Kates1, Monika Gräser1,2,24, Rachel Würstlein25, Steven Shak26, Frederick Baehner26, Hans H Kreipe6, Nadia Harbeck1,25. 1. West German Study Group, Moenchengladbach, Germany. 2. Ev. Bethesda Hospital, Breast Center Niederrhein, Moenchengladbach, Germany. 3. University Clinics Cologne, Women's Clinic and Breast Center, Cologne, Germany. 4. Breast Unit, Kliniken Essen-Mitte, Essen, Germany. 5. Clinic for Gynecology with Breast Center, Charité-Universitätsmedizin Berlin, Berlin, Germany. 6. Medical School Hannover, Institute for Pathology, Hannover, Germany. 7. Department of Gynecology, Breast Center, Red Cross Hospital Munich, Munich, Germany. 8. University Clinics Essen, Women's Clinic, Essen, Germany. 9. University Clinics Leipzig, Women's Clinic, Leipzig, Germany. 10. Niels Stensen Clinics, Clinics for Oncology, Osnabrück, Germany. 11. Oncology Practice Network Troisdorf, Troisdorf, Germany. 12. University Clinics Tübingen, Women's Clinic, Tuebingen, Germany. 13. St Elisabeth Hospital, Cologne, Germany. 14. Luisenhospital Duesseldorf, Practice for Senologic Oncology, Duesseldorf, Germany. 15. University Clinics Aachen, Women's Clinic, Aachen, Germany. 16. Ev. Hospital Bergisch Gladbach, Bergisch Gladbach, Germany. 17. Markus Hospital, Breast Center, Frankfurt, Germany. 18. Ev. Waldkrankenhaus Berlin, Berlin, Germany. 19. Gynecologists at Bahnhofsplatz, Hildesheim, Germany. 20. City Hospital Holweide, Breast Center, Cologne, Germany. 21. Ev. Hospital Gelsenkirchen, Gelsenkirchen, Germany. 22. Institute of Biostatistics and Registry Research, Brandenburg Medical School Theodor Fontane, Neuruppin, Germany. 23. Faculty of Health Sciences, Joint Faculty of the Brandenburg University of Technology Cottbus - Senftenberg, the Brandenburg Medical School Theodor Fontane and the University of Potsdam, Neuruppin, Germany. 24. Department of Gynecology, University Medical Center Hamburg, Hamburg, Germany. 25. Breast Center, Department of Obstetrics and Gynecology and CCC Munich, LMU University Hospital, Munich, Germany. 26. Exact Science, Inc, Redwood City, CA.
Abstract
PURPOSE: To our knowledge, WSG-ADAPT-HR+/HER2- (ClinicalTrials.gov identifier: NCT01779206; n = 5,625 registered) is the first trial combining the 21-gene expression assay (recurrence score [RS]) and response to 3-week preoperative endocrine therapy (ET) to guide systemic therapy in early breast cancer. MATERIALS AND METHODS: Baseline and postendocrine Ki67 (Ki67post) were evaluated centrally. In the endocrine trial, all patients received exclusively ET: patients with pathologic regional lymph node status (pN) 0-1 (ie, 0-3 involved lymph nodes) entered control arm if RS ≤ 11 and experimental arm if RS12-25 with ET response (Ki67post ≤ 10%). All other patients (including N0-1 RS12-25 without ET response) received dose-dense chemotherapy (CT) followed by ET in the CT trial. Primary end point of the endocrine trial was noninferiority of 5-year invasive disease-free survival (5y-iDFS) in experimental (v control) arm; secondary end points included distant DFS, overall survival, and translational research. RESULTS: Intention-to-treat population comprised 2,290 patients (n = 1,422 experimental v n = 868 control): 26.3% versus 34.6% premenopausal and 27.4% versus 24.0% pN1. One-sided 95% lower confidence limit of the 5y-iDFS difference was -3.3%, establishing prespecified noninferiority (P = .05). 5y-iDFS was 92.6% (95% CI, 90.8 to 94.0) in experimental versus 93.9% (95% CI, 91.8 to 95.4) in control arm; 5-year distant DFS was 95.6% versus 96.3%, and 5-year overall survival 97.3% versus 98.0%, respectively. Differences were similar in age and nodal subgroups. In N0-1 RS12-25, outcome of ET responders (ET alone) was comparable with that of ET nonresponders (CT) for age > 50 years and superior for age ≤ 50 years. ET response was more likely with aromatase inhibitors (mostly postmenopausal) than with tamoxifen (mostly premenopausal): 78.1% versus 41.1% (P < .001). ET response was 78.8% in RS0-11, 62.2% in RS12-25, and 32.7% in RS > 25 (n = 4,203, P < .001). CONCLUSION: WSG-ADAPT-HR+/HER2- demonstrates that guiding systemic treatment by both RS and ET response is feasible in clinical routine and spares CT in pre- and postmenopausal patients with ≤ 3 involved lymph nodes.
PURPOSE: To our knowledge, WSG-ADAPT-HR+/HER2- (ClinicalTrials.gov identifier: NCT01779206; n = 5,625 registered) is the first trial combining the 21-gene expression assay (recurrence score [RS]) and response to 3-week preoperative endocrine therapy (ET) to guide systemic therapy in early breast cancer. MATERIALS AND METHODS: Baseline and postendocrine Ki67 (Ki67post) were evaluated centrally. In the endocrine trial, all patients received exclusively ET: patients with pathologic regional lymph node status (pN) 0-1 (ie, 0-3 involved lymph nodes) entered control arm if RS ≤ 11 and experimental arm if RS12-25 with ET response (Ki67post ≤ 10%). All other patients (including N0-1 RS12-25 without ET response) received dose-dense chemotherapy (CT) followed by ET in the CT trial. Primary end point of the endocrine trial was noninferiority of 5-year invasive disease-free survival (5y-iDFS) in experimental (v control) arm; secondary end points included distant DFS, overall survival, and translational research. RESULTS: Intention-to-treat population comprised 2,290 patients (n = 1,422 experimental v n = 868 control): 26.3% versus 34.6% premenopausal and 27.4% versus 24.0% pN1. One-sided 95% lower confidence limit of the 5y-iDFS difference was -3.3%, establishing prespecified noninferiority (P = .05). 5y-iDFS was 92.6% (95% CI, 90.8 to 94.0) in experimental versus 93.9% (95% CI, 91.8 to 95.4) in control arm; 5-year distant DFS was 95.6% versus 96.3%, and 5-year overall survival 97.3% versus 98.0%, respectively. Differences were similar in age and nodal subgroups. In N0-1 RS12-25, outcome of ET responders (ET alone) was comparable with that of ET nonresponders (CT) for age > 50 years and superior for age ≤ 50 years. ET response was more likely with aromatase inhibitors (mostly postmenopausal) than with tamoxifen (mostly premenopausal): 78.1% versus 41.1% (P < .001). ET response was 78.8% in RS0-11, 62.2% in RS12-25, and 32.7% in RS > 25 (n = 4,203, P < .001). CONCLUSION: WSG-ADAPT-HR+/HER2- demonstrates that guiding systemic treatment by both RS and ET response is feasible in clinical routine and spares CT in pre- and postmenopausal patients with ≤ 3 involved lymph nodes.
Authors: Manfred Welslau; Volkmar Müller; Diana Lüftner; Florian Schütz; Elmar Stickeler; Peter A Fasching; Wolfgang Janni; Christoph Thomssen; Isabell Witzel; Tanja N Fehm; Erik Belleville; Simon Bader; Katharina Seitz; Michael Untch; Marc Thill; Hans Tesch; Nina Ditsch; Michael P Lux; Bahriye Aktas; Maggie Banys-Paluchowski; Andreas Schneeweiss; Nadia Harbeck; Rachel Würstlein; Andreas D Hartkopf; Achim Wöckel; Barbara Seliger; Chiara Massa; Hans-Christian Kolberg Journal: Geburtshilfe Frauenheilkd Date: 2022-06-03 Impact factor: 2.754