Early versus deferred use of CDK4/6 inhibitors in advanced breast cancer: circulating tumor DNA analysis of a randomized phase 3 trial.

The phase 3 SONIA trial compared the addition of CDK4/6i to first- versus second-line endocrine therapy for time to disease progression after second-line treatment (progression-free survivalafter two lines of treatment (PFS2)), as well as for secondary outcomes overall survival, PFS after one line of treatment (PFS1), health-related quality of life (HRQOL), toxicity and cost-effectiveness.

第三阶段SONIA试验比较了将CDK4/6i添加到一线与二线内分泌治疗中，对于二线治疗后疾病进展时间（二线治疗后无进展生存期（PFS2））的影响，以及对于次要结果总生存期、一线治疗后无进展生存期（PFS1）、健康相关生活质量（HRQOL）、毒性和成本效益的影响。

No significant difference in PFS2 was observed; however, on an individual patient level this may be different.

未观察到无进展生存期2（PFS2）有显著差异；然而，在个别患者层面上，情况可能会有所不同。

Using prespecified circulating tumor DNA analyses, we performed an exploratory study to evaluate whether pretreatment circulating tumor DNA (ctDNA) levels in plasma can identify patients that benefit from CDK4/6i during their first-line treatment.

我们使用预先设定的循环肿瘤DNA（ctDNA）分析，进行了一项探索性研究，以评估在一线治疗期间，血浆中的基线循环肿瘤DNA（ctDNA）水平是否能识别出从CDK4/6抑制剂中获益的患者。

Cell free DNA before start of first-line treatment from 409 female patients participating in SONIA was analyzed with the modified fast aneuploidy screening test-sequencing system.

在SONIA研究中，对409名参与的女性患者在一线治疗开始前进行了游离DNA分析，使用的是改良快速非整倍体筛查测试-测序系统。

This assay yields a genome-wide aneuploidy score, indicative of ctDNA levels.

该检测产生一个全基因组非整倍体评分，指示ctDNA水平。

Cox proportional hazard analyses for PFS1 and PFS2 were performed separately for the ctDNA high group (aneuploidy score ≥ 5) and the ctDNA low group (aneuploidy score < 5).

Cox比例风险分析分别对ctDNA高组（染色体非整倍体评分≥5）和ctDNA低组（染色体非整倍体评分<5）的无进展生存期1（PFS1）和无进展生存期2（PFS2）进行了单独分析。

In total, 141 of the 409 included patients had a high genome-wide aneuploidy score at baseline.

在总共409名纳入的患者中，有141名患者在基线时具有高全基因组非整倍体评分。

PFS2 in the first- compared to the second-line CDK4/6i strategy showed hazard ratios of 0.58 (95% confidence interval0.38-0.88) and 1.36 (95% confidence interval0.95-1.96) in the high and low aneuploidy group, respectively.

一线与二线CDK4/6i策略的PFS2比较显示，高异倍体组和低异倍体组的风险比分别为0.58（95%置信区间0.38-0.88）和1.36（95%置信区间0.95-1.96）。

A significant interaction was demonstrated between treatment strategy and aneuploidy score for PFS2 (P = 0.004).

治疗策略与异倍体评分对于PFS2的显著相互作用得到了证实（P = 0.004）。

In conclusion, this study demonstrated that pretreatment ctDNA levels can be used to identify patients that benefit from first-line CDK4/6i treatment.

总之，本研究证明了治疗前循环肿瘤DNA（ctDNA）水平可用于识别从一线CDK4/6抑制剂治疗中获益的患者。

ClinicalTrials.gov registration: NCT03425838 .

ClinicalTrials.gov注册信息：NCT03425838。