Ribociclib Plus Endocrine Therapy in Hormone Receptor-Positive/ERBB2-Negative Early Breast Cancer: 4-Year Outcomes From the NATALEE Randomized Clinical Trial.

Evaluating the efficacy and safety of adjuvant ribociclib beyond the planned 3-year treatment period is critical for understanding the long-term impact on recurrences.

评估辅助治疗中利博西利超过计划的3年治疗期的疗效和安全性对于理解其对复发长期影响至关重要。

Background

To evaluate efficacy and safety of adjuvant ribociclib in an exploratory 4-year analysis of the NATALEE (New Adjuvant Trial With Ribociclib [LEE011]) randomized clinical trial, with all patients no longer receiving ribociclib treatment.

为了评估辅助性利博西利在NATALEE（新辅助性利博西利[LEE011]）随机临床试验的探索性4年分析中的疗效和安全性，所有患者已不再接受利博西利治疗。

DESIGN, SETTING, AND PARTICIPANTS: This exploratory analysis of an international, open-label, randomized phase 3 trial analyzed adjuvant treatment for premenopausal and postmenopausal women and men with hormone receptor-positive/ERBB2-negative early breast cancer.

设计、设置和参与者：这项国际开放标签的随机III期试验的探索性分析，分析了对绝经前和绝经后女性及男性激素受体阳性/ERBB2阴性早期乳腺癌患者的辅助治疗。

Eligible patients had anatomic stage IIA (either N0 with additional risk factors or N1 [1-3 axillary lymph nodes]), IIB, or III disease per the American Joint Committee on Cancer Staging Manual, eighth edition.

符合条件的患者具有美国癌症联合委员会分期手册第8版规定的解剖学分期IIA期（无N0但有额外风险因素或N1[1-3腋窝淋巴结]）、IIB期或III期疾病。

The data cutoff date was April 29, 2024.

数据截止日期为2024年4月29日。

Methods

Patients were randomized 1:1 to receive ribociclib (400 mg once daily, days 1-21 of a 28-day cycle, over 36 months) plus NSAI (letrozole, 2.5 mg, or anastrozole, 1 mg, once daily continuously for 60 months) or NSAI alone.

患者按1:1的比例随机接受利伯西利布（每日400毫克，第1-21天，28天为一个周期，持续36个月）联合NSAI（来曲唑2.5毫克或阿那曲唑1毫克，每日一次，持续60个月）或仅接受NSAI治疗。

Men and premenopausal women also received goserelin (3.6 mg once every 28 days administered subcutaneously).

男性和绝经前女性患者还接受了戈舍瑞林（每28天皮下注射3.6毫克）。

main_outcomes_and_measures

The primary end point was iDFS, and secondary efficacy end points included distant disease-free survival, recurrence-free survival, and overall survival. Survival was evaluated by the Kaplan-Meier method.

主要终点是无浸润性疾病生存期（iDFS），次要疗效终点包括无远处疾病生存期、无复发生存期和总生存期。生存期通过Kaplan-Meier方法进行评估。

Results

Among 5101 patients included in the analysis (median [range] age, 52 [24-90] years; 5081 [99.6%] female), the median follow-up for iDFS was 44.2 months (range, 0-63 months).

分析纳入了5101名患者（中位年龄[范围]为52[24-90]岁；5081名[99.6%]为女性），iDFS的中位随访时间为44.2个月（范围，0-63个月）。

Ribociclib plus NSAI continued to show iDFS benefit over NSAI alone (hazard ratio, 0.72; 95% CI, 0.61-0.84), with 3-year iDFS rates of 90.8% vs 88.1% (difference, 2.7 percentage points) and 4-year rates of 88.5% vs 83.6% (difference, 4.9 percentage points).

利博西利联合NSAI继续显示出比单独使用NSAI更好的无侵袭性疾病生存（iDFS）获益（风险比，0.72；95% 置信区间，0.61-0.84），3年iDFS率分别为90.8%和88.1%（差异，2.7个百分点），4年iDFS率分别为88.5%和83.6%（差异，4.9个百分点）。

The efficacy benefit was consistent across subgroups and secondary end points.

疗效获益在各个亚组和次要终点中保持一致。

Overall survivaldata remain immature, although a trend in favor of ribociclib plus NSAI over NSAI alone was observed (hazard ratio, 0.83; 95% CI, 0.64-1.07).

尽管观察到利博西利联合NSAI相对于单独NSAI的总生存趋势有利（风险比，0.83；95%置信区间，0.64-1.07），但总生存数据尚不成熟。

The incidenceof adverse events has remained stable.

不良事件的发生率保持稳定。

conclusions_and_relevance

This exploratory analysis of the NATALEE randomized clinical trial, with a median follow-up beyond the 3-year treatment duration, demonstrated consistent iDFS benefit with ribociclib plus NSAI over NSAI alone.

这项对NATALEE随机临床试验的探索性分析，随访中位时间超过3年的治疗期，显示了利伯西利联合NSAI与单独使用NSAI相比，无侵袭性疾病生存（iDFS）的益处是一致的。

trial_registration

ClinicalTrials.gov Identifier: NCT03701334.

ClinicalTrials.gov注册号：NCT03701334。