Hortobagyi G N, Lacko A, Sohn J, Cruz F, Ruiz Borrego M, Manikhas A, Hee Park Y, Stroyakovskiy D, Yardley D A, Huang C-S, Fasching P A, Crown J, Bardia A, Chia S, Im S-A, Martin M, Loi S, Xu B, Hurvitz S, Barrios C, Untch M, Moroose R, Visco F, Parnizari F, Zarate J P, Li Z, Waters S, Chakravartty A, Slamon D
Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
Dolnoslaskie Centrum Onkologii, Wroclaw, Poland.
Ann Oncol. 2025 Feb;36(2):149-157. doi: 10.1016/j.annonc.2024.10.015. Epub 2024 Oct 21.
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).
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.
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.
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.
NATALEE研究评估了在广泛的激素受体（HR）阳性/人表皮生长因子2（HER2）阴性早期乳腺癌患者群体中，与单独使用非甾体芳香化酶抑制剂（NSAI）相比，3年辅助性瑞博西尼联合NSAI的疗效和耐受性，其中包括一组无淋巴结受累的特定患者群体。这是对无侵袭性疾病生存期（iDFS）的最终预先计划分析。
绝经前/绝经后女性及男性按1:1随机分组，分别接受瑞博西尼（n = 2549；400mg/天，3周用药/1周停药，共36个月）联合NSAI（来曲唑2.5mg/天或阿那曲唑1mg/天，共60个月）或单独使用NSAI（n = 2552）。男性和绝经前女性还接受戈舍瑞林（每28天一次，3.6mg）。患者的解剖分期为IIA期（N0且有其他危险因素或N1）、IIB期或III期疾病。主要终点是iDFS。次要疗效终点是无复发生存期（RFS）、远处无病生存期（distant DFS）和总生存期。此次最终的iDFS分析是在约500例事件发生后进行计划的。
在数据截止时（2023年7月21日），1996例患者（78.3%）停止使用瑞博西尼；1091例（42.8%）完成了3年的瑞博西尼治疗，528例（20.7%）仍在接受瑞博西尼治疗。iDFS的中位随访时间为33.3个月。总体而言，瑞博西尼联合NSAI组和单独使用NSAI组分别发生226例和283例iDFS事件。瑞博西尼联合NSAI组相对于单独使用NSAI组在iDFS方面显示出显著获益[风险比0.749，95%置信区间（CI）0.628 - 0.892；P = 0.0012]。3年iDFS率分别为90.7%（95%CI 89.3%至91.8%）和87.6%（95%CI 86.1%至88.9%）。在预先设定的亚组中，包括分期（II/III）和淋巴结状态（阳性/阴性），均观察到一致的获益。远处DFS和RFS更倾向于瑞博西尼联合NSAI组。总生存期数据尚不成熟。未观察到新的安全信号。
随着随访时间延长且大多数患者停用瑞博西尼，NATALEE研究继续表明，在总体人群及关键亚组中，瑞博西尼联合NSAI相对于单独使用NSAI在iDFS方面具有获益。观察到的不良事件保持稳定。
