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

TY - JOUR

T1 - Endocrine Therapy Response and 21-Gene Expression Assay for Therapy Guidance in HR+/HER2- Early Breast Cancer

AU - Nitz, Ulrike A

AU - Gluz, Oleg

AU - Kümmel, Sherko

AU - Christgen, Matthias

AU - Braun, Michael

AU - Aktas, Bahriye

AU - Lüdtke-Heckenkamp, Kerstin

AU - Forstbauer, Helmut

AU - Grischke, Eva-Maria

AU - Schumacher, Claudia

AU - Darsow, Maren

AU - Krauss, Katja

AU - Nuding, Benno

AU - Thill, Marc

AU - Potenberg, Jochem

AU - Uleer, Christoph

AU - Warm, Mathias

AU - Fischer, Hans Holger

AU - Malter, Wolfram

AU - Hauptmann, Michael

AU - Kates, Ronald E

AU - Gräser, Monika

AU - Würstlein, Rachel

AU - Shak, Steven

AU - Baehner, Frederick

AU - Kreipe, Hans H

AU - Harbeck, Nadia

PY - 2022/8/10

Y1 - 2022/8/10

N2 - 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.

AB - 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.

KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use

KW - Breast Neoplasms/drug therapy

KW - Chemotherapy, Adjuvant

KW - Disease-Free Survival

KW - Female

KW - Gene Expression Profiling

KW - Humans

KW - Ki-67 Antigen

KW - Middle Aged

KW - Receptor, ErbB-2/metabolism

KW - Tamoxifen/therapeutic use

U2 - 10.1200/JCO.21.02759

DO - 10.1200/JCO.21.02759

M3 - SCORING: Journal article

C2 - 35404683

VL - 40

SP - 2557

EP - 2567

JO - J CLIN ONCOL

JF - J CLIN ONCOL

SN - 0732-183X

IS - 23

ER -