Overall Survival With First-Line vs Second-Line CDK4/6 Inhibitor Use in Advanced Breast Cancer: A Randomized Clinical Trial.

The SONIA trial evaluates the optimal timing of CDK4/6i administration, either in first-line or second-line setting.

SONIA试验评估了CDK4/6i的最佳给药时机，无论是在一线还是二线治疗中。

Background

To determine whether first-line CDK4/6i use is superior to second-line use in terms of overall survival(OS) and to provide an updated analysis of the primary end point of progression-free survival(PFS) after 2 lines of therapy.

确定一线CDK4/6i使用是否在总生存（OS）方面优于二线使用，并提供在两线治疗后无进展生存期（PFS）主要终点的更新分析。

DESIGN, SETTING, AND PARTICIPANTS: The phase 3 SONIA randomized clinical trial is a multicenter trial in the Netherlands.

设计、环境和参与者：SONIA第三阶段随机临床试验是一项在荷兰进行的多中心试验。

Patients with HR-positive, ERBB2-negative ABC who did not receive prior treatment for ABC were randomized 1:1 to receive CDK4/6i added to first-line or second-line endocrine therapy.

HR阳性、ERBB2阴性的ABC患者，如果之前未接受过ABC治疗，将按1:1的比例随机接受CDK4/6i联合一线或二线内分泌治疗。

Patients were enrolled between November 23, 2017, and September 1, 2021.

患者入组时间为2017年11月23日至2021年9月1日。

Data cutoff for this prespecified updated analysis was September 1, 2024.

本次预先设定的更新分析的数据截止日期为2024年9月1日。

Data were analyzed from February to May 2025.

数据分析的时间范围是从2025年2月至5月。

Methods

Aromatase inhibitor plus CDK4/6i as first-line treatment followed by fulvestrant as second-line treatment (CDK4/6i first-line group) vs aromatase inhibitor as first-line treatment followed by fulvestrant plus CDK4/6i as second-line treatment (CDK4/6i second-line group).

芳香酶抑制剂联合CDK4/6抑制剂作为一线治疗，随后使用fulvestrant作为二线治疗（CDK4/6抑制剂一线组）与芳香酶抑制剂作为一线治疗，随后使用fulvestrant联合CDK4/6抑制剂作为二线治疗（CDK4/6抑制剂二线组）。

main_outcomes_and_measures

The primary end point was PFS after 2 lines of therapy.

主要终点是两线治疗后的无进展生存期（PFS）。

OS was a key secondary end point, with a prespecified analysis when all patients had 3 or more years of follow-up.

总生存（OS）是一个关键的次要终点，当所有患者有3年或以上的随访时进行了预先规定的分析。

Results

Of 1050 enrolled patients, the median (IQR) age was 64 (16) years.

在1050名入组患者中，中位年龄（四分位数间距）为64（16）岁。

A total of 524 were randomized to the CDK4/6i first-line group and 526 patients to the CDK4/6i second-line group.

共有524名患者被随机分配到CDK4/6抑制剂一线治疗组，526名患者被分配到CDK4/6抑制剂二线治疗组。

At a median follow-up of 58.5 months (95% CI, 57.0-60.9), 606 deaths (57.7%) had occurred.

在中位随访58.5个月（95%置信区间，57.0-60.9）时，共有606例（57.7%）患者死亡。

The median OS was 47.9 months (95% CI, 44.0-54.3) with first-line CDK4/6i and 48.1 months (95% CI, 44.7-52.0) with second-line CDK4/6i (hazard ratio[HR], 0.91; 95% CI, 0.77-1.07; P = .24).

一线使用CDK4/6i的中位总生存期为47.9个月（95%置信区间，44.0-54.3），二线使用CDK4/6i的中位总生存期为48.1个月（95%置信区间，44.7-52.0）（风险比[HR]，0.91；95%置信区间，0.77-1.07；P = .24）。

A post hoc subgroup analysis suggested an OS benefit with first-line use in premenopausal patients (HR, 0.53; 95% CI, 0.32-0.87) but not in postmenopausal patients (HR, 1.00; 95% CI, 0.84-1.19; P for interaction = .01).

事后亚组分析表明，一线使用CDK4/6i在绝经前患者中显示出总生存期的益处（HR，0.53；95%置信区间，0.32-0.87），但在绝经后患者中没有显示出这种益处（HR，1.00；95%置信区间，0.84-1.19；交互作用P值 = .01）。

Among patients who discontinued second-line treatment, 257 of 303 in the first-line group (84.8%) and 303 of 360 in the second-line group (84.2%) received subsequent anticancer therapy, with similar treatment patterns.

在停用二线治疗的患者中，一线组的303名患者中有257名（84.8%），二线组的360名患者中有303名（84.2%）接受了后续的抗癌治疗，治疗模式相似。

First-line CDK4/6i use was associated with more grade 3 or higher adverse events than second-line use (3400 vs 2242, respectively).

一线使用CDK4/6抑制剂与二线使用相比，与更多3级或更高级别的不良事件相关（分别为3400例和2242例）。

conclusions_and_relevance

In this phase 3 randomized clinical trial, first-line CDK4/6i use did not improve OS compared with second-line use but did increase treatment-related toxic effects.

在这项III期随机临床试验中，一线使用CDK4/6抑制剂并未改善总生存期，与二线使用相比，但增加了治疗相关的毒性效应。

Post hoc analysis suggests an OS benefit with first-line use in premenopausal patients.

事后分析表明，在绝经前患者中，一线使用CDK4/6抑制剂可能带来总生存期的益处。

trial_registration

ClinicalTrials.gov Identifier: NCT03425838.

临床试验注册号：NCT03425838。