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
- Author(s)
- Slamon, DJ; Fasching, PA; Hurvitz, S; Chia, S; Crown, J; Martin, 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;
- Journal Title
- Therapeutic Advances in Medical Oncology
- Publication Type
- Protocol
- 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).
- Publisher
- Sage
- Keywords
- CDK4/6 inhibitors; HR+/HER2- early breast cancer; Natalee; adjuvant therapy; ribociclib
- Department(s)
- Medical Oncology; Laboratory Research
- PubMed ID
- 37275963
- Publisher's Version
- https://doi.org/10.1177/17588359231178125
- Open Access at Publisher's Site
https://doi.org/10.1177/17588359231178125- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2023-09-05 06:33:29
Last Modified: 2023-09-05 06:34:32