A phase III trial of adjuvant ribociclib plus endocrine therapy versus endocrine therapy alone in patients with HR-positive/HER2-negative early breast cancer: final invasive disease-free survival results from the NATALEE trial

Hortobagyi GN, Lacko A, Sohn J, Cruz F, Ruiz Borrego M, Manikhas A, Hee Park Y, Stroyakovskiy D, Yardley DA, Huang CS, Fasching P, Crown J, Bardia A, Chia S, Im SA, Martin M, Loi S, Xu B, Hurvitz S, Barrios C, Untch M, Moroose R, Visco F, Parnizari F, Zarate JP, Li Z, Waters S, Chakravartty A, Slamon D (2025)

Publication Language: English

Publication Type: Journal article

Publication year: 2025

Journal

Book Volume: 36

Pages Range: 149-157

Journal Issue: 2

DOI: 10.1016/j.annonc.2024.10.015

Abstract

Background: NATALEE assessed efficacy and tolerability of 3 years of adjuvant ribociclib plus a nonsteroidal aromatase inhibitor (NSAI) compared with an NSAI alone in a broad population of patients with hormone receptor (HR)-positive/human epidermal growth factor 2 (HER2)-negative early breast cancer, including a select group without nodal involvement. This is the final preplanned analysis of invasive disease-free survival (iDFS). Patients and methods: Premenopausal/postmenopausal women and men were randomized 1 : 1 to ribociclib (n = 2549; 400 mg/day, 3 weeks on/1 week off for 36 months) plus NSAI (letrozole 2.5 mg/day or anastrozole 1 mg/day for 60 months) or NSAI alone (n = 2552). Men and premenopausal women also received goserelin (3.6 mg once every 28 days). Patients had anatomical stage IIA (N0 with additional risk factors or N1), IIB, or III disease. The primary endpoint was iDFS. Secondary efficacy endpoints were recurrence-free survival (RFS), distant DFS, and overall survival. This final iDFS analysis was planned after ∼500 events. Results: At data cut-off (21 July 2023), ribociclib was stopped for 1996 patients (78.3%); 1091 (42.8%) completed 3 years of ribociclib, and ribociclib treatment was ongoing for 528 (20.7%). Median follow-up for iDFS was 33.3 months. Overall, 226 and 283 iDFS events occurred with ribociclib plus NSAI versus NSAI alone, respectively. Ribociclib plus NSAI demonstrated significant iDFS benefit over NSAI alone [hazard ratio 0.749, 95% confidence interval (CI) 0.628-0.892; P = 0.0012]. The 3-year iDFS rates were 90.7% (95% CI 89.3% to 91.8%) versus 87.6% (95% CI 86.1% to 88.9%). A consistent benefit was observed across prespecified subgroups, including stage (II/III) and nodal status (positive/negative). Distant DFS and RFS favored ribociclib plus NSAI. Overall survival data were immature. No new safety signals were observed. Conclusions: With longer follow-up and most patients off ribociclib, NATALEE continues to demonstrate iDFS benefit with ribociclib plus NSAI over NSAI alone in the overall population and across key subgroups. Observed adverse events remained stable.

Authors with CRIS profile

Involved external institutions

Novartis AG Switzerland (CH) HELIOS Kliniken Germany (DE) Peking Union Medical College / 北京协和医学院 China (CN) Orlando Health United States (USA) (US) LACOG - Latin American Cooperative Oncology Group Brazil (BR) University of Washington United States (USA) (US) Columbian College of Arts and Sciences United States (USA) (US) TRIO - Translational Research In Oncology Canada (CA) Novartis Ireland Limited Ireland (IE) Peter MacCallum Cancer Centre Australia (AU) Lower Silesia Oncology Centre / Dolnośląskie Centrum Onkologii we Wrocławiu Poland (PL) University of Texas MD Anderson Cancer Center United States (USA) (US) Severance Hospital / 세브란스 병원 Korea, Republic of (KR) Instituto Brasileiro de Controle do Câncer (IBCC) Brazil (BR) City Clinical Oncology Center (CCOC) / Городской клинический онкологический диспансер Russian Federation (RU) Hospitales Universitarios Virgen Macarena y Virgen del Rocío Spain (ES) Sungkyunkwan University (SKKU) Korea, Republic of (KR) National Taiwan University Hospital (NTUH) / 國立台灣大學醫學院附設醫院 Taiwan (TW) Moscow City Oncology Hospital №62 Russian Federation (RU) Sarah Cannon Research Institute (SCRI) United States (USA) (US) St Vincent’s Private Hospital Ireland (IE) British Columbia Cancer Agency Canada (CA) Universidad Complutense de Madrid (UCM) Spain (ES) University of California Los Angeles (UCLA) United States (USA) (US) Seoul National University (SNU) / 서울대학교 Korea, Republic of (KR)

How to cite

APA:

Hortobagyi, G.N., Lacko, A., Sohn, J., Cruz, F., Ruiz Borrego, M., Manikhas, A.,... Slamon, D. (2025). A phase III trial of adjuvant ribociclib plus endocrine therapy versus endocrine therapy alone in patients with HR-positive/HER2-negative early breast cancer: final invasive disease-free survival results from the NATALEE trial. Annals of Oncology, 36(2), 149-157. https://doi.org/10.1016/j.annonc.2024.10.015

MLA:

Hortobagyi, G. N., et al. "A phase III trial of adjuvant ribociclib plus endocrine therapy versus endocrine therapy alone in patients with HR-positive/HER2-negative early breast cancer: final invasive disease-free survival results from the NATALEE trial." Annals of Oncology 36.2 (2025): 149-157.

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