Rationale and trial design of NATALEE: a Phase III trial of adjuvant ribociclib + endocrine therapy versus endocrine therapy alone in patients with HR+/HER2− early breast cancer

Slamon DJ, Fasching PA, Hurvitz S, Chia S, Crown J, Martín M, Barrios CH, Bardia A, Im SA, Yardley DA, Untch M, Huang CS, Stroyakovskiy D, Xu B, Moroose RL, Loi S, Visco F, Bee-Munteanu V, Afenjar K, Fresco R, Taran T, Chakravartty A, Zarate JP, Lteif A, Hortobagyi GN (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Book Volume: 15

DOI: 10.1177/17588359231178125

Abstract

Background: Ribociclib has demonstrated a statistically significant overall survival benefit in pre- and postmenopausal patients with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2−) advanced breast cancer. New Adjuvant Trial with Ribociclib [LEE011] (NATALEE) is a trial evaluating the efficacy and safety of adjuvant ribociclib plus endocrine therapy (ET) versus ET alone in patients with HR+/HER2− early nonmetastatic breast cancer (EBC). Methods/design: NATALEE is a multicenter, randomized, open-label, Phase III trial in patients with HR+/HER2− EBC. Eligible patients include women, regardless of menopausal status, and men aged ⩾18 years. Select patients with stage IIA, stage IIB, or stage III disease (per the anatomic classification in the AJCC Cancer Staging Manual, 8th edition) with an initial diagnosis ⩽18 months prior to randomization are eligible. Patients receiving standard (neo)adjuvant ET are eligible if treatment was initiated ⩽12 months before randomization. Patients undergo 1:1 randomization to ribociclib 400 mg/day (3 weeks on/1 week off) +ET (letrozole 2.5 mg/day or anastrozole 1 mg/day [investigator’s discretion] plus goserelin [men or premenopausal women]) or ET alone. Ribociclib treatment duration is 36 months; ET treatment duration is ⩾60 months. The primary end point is invasive disease-free survival. Discussion: The 36-month treatment duration of ribociclib in NATALEE is extended compared with that in other adjuvant cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor trials and is intended to maximize efficacy due to longer duration of CDK4/6 inhibition. Compared with the 600-mg/day dose used in advanced breast cancer, the reduced ribociclib dose used in NATALEE may improve tolerability while maintaining efficacy. NATALEE includes the broadest population of patients with HR+/HER2− EBC of any Phase III trial currently evaluating adjuvant CDK4/6 inhibitor treatment. Trial registration: ClinicalTrials.gov identifier: NCT03701334 (https://clinicaltrials.gov/ct2/show/NCT03701334)

Involved external institutions

University of California Los Angeles (UCLA) United States (USA) (US) Sarah Cannon Research Institute (SCRI) United States (USA) (US) Moscow City Oncology Hospital №62 Russian Federation (RU) Columbian College of Arts and Sciences United States (USA) (US) Novartis AG Switzerland (CH) HELIOS Kliniken Germany (DE) St Vincent's University Hospital Ireland (IE) Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS) Brazil (BR) Seoul National University (SNU) / 서울대학교 Korea, Republic of (KR) Peking Union Medical College Hospital (PUMCH) / Beijing Xiehe Hospital China (CN) British Columbia Cancer Agency Canada (CA) Orlando Health United States (USA) (US) Veterans Affairs Healthcare System Boston and Harvard Medical School United States (USA) (US) University of Texas MD Anderson Cancer Center United States (USA) (US) Peter MacCallum Cancer Centre Australia (AU) National Taiwan University Hospital (NTUH) / 國立台灣大學醫學院附設醫院 Taiwan (TW) TRIO - Translational Research In Oncology Canada (CA) Universidad Complutense de Madrid (UCM) Spain (ES)

How to cite

APA:

Slamon, D.J., Fasching, P.A., Hurvitz, S., Chia, S., Crown, J., Martín, M.,... Hortobagyi, G.N. (2023). Rationale and trial design of NATALEE: a Phase III trial of adjuvant ribociclib + endocrine therapy versus endocrine therapy alone in patients with HR+/HER2− early breast cancer. Therapeutic Advances in Medical Oncology, 15. https://dx.doi.org/10.1177/17588359231178125

MLA:

Slamon, Dennis J., et al. "Rationale and trial design of NATALEE: a Phase III trial of adjuvant ribociclib + endocrine therapy versus endocrine therapy alone in patients with HR+/HER2− early breast cancer." Therapeutic Advances in Medical Oncology 15 (2023).

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