NATALEE研究的原理与试验设计：一项针对HR+/HER2-早期乳腺癌患者的辅助性瑞博西尼联合内分泌治疗与单纯内分泌治疗的III期试验。

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

作者信息

Slamon Dennis J, Fasching Peter A, Hurvitz Sara, Chia Stephen, Crown John, Martín Miguel, Barrios Carlos H, Bardia Aditya, Im Seock-Ah, Yardley Denise A, Untch Michael, Huang Chiun-Sheng, Stroyakovskiy Daniil, Xu Binghe, Moroose Rebecca L, Loi Sherene, Visco Frances, Bee-Munteanu Valerie, Afenjar Karen, Fresco Rodrigo, Taran Tetiana, Chakravartty Arunava, Zarate Juan Pablo, Lteif Agnes, Hortobagyi Gabriel N

机构信息

David Geffen School of Medicine at UCLA, 10945 Le Conte Ave. Suite 3360, Los Angeles, CA 90095, USA.

University Hospital Erlangen Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.

出版信息

Ther Adv Med Oncol. 2023 May 29;15:17588359231178125. doi: 10.1177/17588359231178125. eCollection 2023.

DOI:10.1177/17588359231178125

PMID:37275963

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10233570/

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) 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 , 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).

摘要

背景

瑞博西尼已在激素受体阳性/人表皮生长因子受体2阴性（HR+/HER2-）的绝经前和绝经后晚期乳腺癌患者中显示出具有统计学意义的总生存获益。瑞博西尼新辅助试验[LEE011]（NATALEE）是一项评估辅助性瑞博西尼加内分泌治疗（ET）与单纯ET相比，在HR+/HER2-早期非转移性乳腺癌（EBC）患者中的疗效和安全性的试验。

方法/设计：NATALEE是一项针对HR+/HER2- EBC患者的多中心、随机、开放标签的III期试验。符合条件的患者包括女性，无论绝经状态如何，以及年龄≥18岁的男性。随机分组前初始诊断≤18个月的IIA期、IIB期或III期疾病（根据第8版的解剖学分类）的特定患者符合条件。如果在随机分组前≤12个月开始接受标准（新）辅助ET治疗，则接受该治疗的患者符合条件。患者按1:1随机分组，分别接受瑞博西尼400mg/天（3周用药/1周停药）+ET（来曲唑2.5mg/天或阿那曲唑1mg/天[由研究者决定]加戈舍瑞林[男性或绝经前女性]）或单纯ET治疗。瑞博西尼治疗持续时间为36个月；ET治疗持续时间≥60个月。主要终点是无侵袭性疾病生存期。

讨论

与其他辅助性细胞周期蛋白依赖性激酶4和6（CDK4/6）抑制剂试验相比，NATALEE中瑞博西尼36个月的治疗持续时间有所延长，旨在通过延长CDK4/6抑制时间来最大化疗效。与晚期乳腺癌中使用的600mg/天剂量相比，NATALEE中使用的降低剂量的瑞博西尼可能在维持疗效的同时提高耐受性。NATALEE纳入了目前评估辅助性CDK4/6抑制剂治疗的任何III期试验中最广泛的HR+/HER2- EBC患者群体。