Endocrine Therapy Response and 21-Gene Expression Assay for Therapy Guidance in HR+/HER2– Early Breast Cancer

Media type: E-Article
Title: Endocrine Therapy Response and 21-Gene Expression Assay for Therapy Guidance in HR+/HER2– Early Breast Cancer
Contributor: Nitz, Ulrike A.; Gluz, Oleg; Kümmel, Sherko; Christgen, Matthias; Braun, Michael; Aktas, Bahriye; Lüdtke-Heckenkamp, Kerstin; Forstbauer, Helmut; Grischke, Eva-Maria; Schumacher, Claudia; Darsow, Maren; Krauss, Katja; Nuding, Benno; Thill, Marc; Potenberg, Jochem; Uleer, Christoph; Warm, Mathias; Fischer, Hans Holger; Malter, Wolfram; Hauptmann, Michael; Kates, Ronald E.; Gräser, Monika; Würstlein, Rachel; Shak, Steven; [...]
imprint: American Society of Clinical Oncology (ASCO), 2022
Published in: Journal of Clinical Oncology
Language: English
DOI: 10.1200/jco.21.02759
ISSN: 0732-183X; 1527-7755
Origination:
Footnote:
Description: <jats:sec><jats:title>PURPOSE</jats:title><jats:p> 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. </jats:p></jats:sec><jats:sec><jats:title>MATERIALS AND METHODS</jats:title><jats:p> Baseline and postendocrine Ki67 (Ki67<jats:sub>post</jats:sub>) 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 (Ki67<jats:sub>post</jats:sub> ≤ 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. </jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p> 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). </jats:p></jats:sec><jats:sec><jats:title>CONCLUSION</jats:title><jats:p> 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. </jats:p></jats:sec>
Access State: Open Access

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