US Food and Drug Administration Approval Summary: Ribociclib With an Aromatase Inhibitor in the Adjuvant Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Stage II and III High-Risk Early Breast Cancer Treatment Setting.

patients_and_methods

The FDA approval was based on NATALEE, a randomized (1:1), open-label, multicenter, multinational trial in adults of any sex or menopausal status with hormone receptor-positive, HER2-negative stage II and III EBC who received ribociclib plus an AI (Ribo + AI, n = 2,549) versus an AI (n = 2,552); patients also received goserelin as clinically indicated.

FDA的批准基于NATALEE试验，这是一项随机（1:1）、开放标签、多中心、多国的试验，涉及任何性别或绝经状态的成年激素受体阳性、HER2阴性的II期和III期EBC患者，这些患者接受了利伯西利布加芳香酶抑制剂（Ribo + AI，n = 2,549）与仅芳香酶抑制剂（n = 2,552）的治疗；患者还根据临床需要接受了戈舍瑞林治疗。

Ribociclib was given at 400 mg once daily (3 weeks on/1 week off) for up to 36 months.

利博西利以每日400毫克（3周服用/1周停药）的方式给药，最多持续36个月。

AI was given per standard of care for at least 5 years.

按照标准治疗方案，至少给予5年的芳香酶抑制剂治疗。

The primary end point was invasive disease-free survival (iDFS), defined according to Standardized Definitions for Efficacy End Points version 1.0 criteria.

主要终点是侵袭性疾病无复发生存期（iDFS），根据标准化的疗效终点定义版本1.0标准进行定义。

Overall survival(OS) was a secondary end point.

总生存（OS）是次要终点。

Results

iDFS was statistically significant at the third interim analysis (IA3; January 2023; hazard ratio[HR], 0.75 [95% CI, 0.62 to 0.91]) in the intent-to treat (ITT) population.

在意向治疗（ITT）人群中，第三次中期分析（IA3；2023年1月；风险比[HR]，0.75 [95% 置信区间，0.62至0.91]）显示无病生存期（iDFS）具有统计学意义。

However, at IA3, there was a large amount of censoring for iDFS as only 20% of patients had completed 3 years of adjuvant therapy and OS was immature.

然而，在第三次中期分析（IA3）时，由于仅有20%的患者完成了3年的辅助治疗，无病生存期（iDFS）存在大量的删失数据，总生存（OS）数据尚不成熟。

Because of these concerns, FDA requested that NATALEE continue until the final iDFS analysis.

鉴于这些担忧，FDA要求NATALEE研究继续进行，直至完成最终的iDFS分析。

At the final iDFS analysis, the iDFS at 36 months was 90.7% (95% CI, 89.3 to 91.8) for Ribo + AI versus 87.6% (95% CI, 86.1 to 88.9) for AI, with a HR of 0.75 (95% CI, 0.63 to 0.89).

在最终的iDFS分析中，36个月时Ribo + AI组的iDFS为90.7%（95%置信区间，89.3至91.8），而AI组为87.6%（95%置信区间，86.1至88.9），风险比为0.75（95%置信区间，0.63至0.89）。

More patients who received ribociclib experienced all-grade (98% Ribo + AI v 88% AI) and grade ≥3 (64% Ribo + AI v 19% AI) adverse reactions (ARs).

更多接受利博西利治疗的患者经历了所有级别的不良反应（98%利博西利+AI对比88%AI）和3级或以上级别的不良反应（64%利博西利+AI对比19%AI）。

Conclusions

Addition of adjuvant ribociclib to NSAI for adults with high-risk stage II and III hormone receptor-positive, HER2-negative EBC demonstrated a favorable benefit-risk profile with a statistically significant iDFS advantage.

将辅助性利博西利添加到NSAI治疗成年人高风险II期和III期激素受体阳性、HER2阴性早期乳腺癌（EBC）中，显示出有利的风险-效益比，并具有统计学意义的无侵袭性疾病生存期（iDFS）优势。

OS data remain immature.

总生存数据尚未成熟。