Role of ctDNA in Predicting the Outcome of Patients with Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer Treated with First-line Ribociclib and Letrozole: BioItaLEE Trial.

experimental_design

A total of 287 patients were enrolled, with ctDNA analyzed at baseline (n = 263), day 15 of cycle 1 (C1D15; n = 238), C2D1 (n = 241), and first imaging (n = 206).

共有287名患者入组，其中在基线期（n = 263）、第1周期第15天（C1D15；n = 238）、第2周期第1天（C2D1；n = 241）和首次影像检查（n = 206）时分析了ctDNA。

The primary objective was to identify ctDNA alterations, characterize their evolution across treatment time points, and assess their association with progression-free survival(PFS).

主要目标是识别循环肿瘤DNA（ctDNA）的改变，描述这些改变在治疗过程中的演变，并评估它们与无进展生存（PFS）之间的关系。

Results

Median PFS was 23.4 months (95% confidence interval, 20.8 to not estimable).

中位无进展生存期为23.4个月（95%置信区间，20.8至无法估计）。

At baseline, the most frequently altered genes were PIK3CA (22.1%) and TP53 (15.5%).

基线时，最常发生改变的基因是PIK3CA（22.1%）和TP53（15.5%）。

Alterations in TP53, MYC, and HER- and cyclin-dependent kinase 4/6- pathway genes were linked to early progression.

TP53、MYC以及HER和细胞周期依赖性激酶4/6通路基因的改变与早期进展相关。

Absence of a detectable mutation at baseline (n = 150, 57%) was associated with a better prognosis [hazard ratio(HR) = 0.41].

基线时未检测到可检测的突变（n = 150, 57%）与更好的预后相关[风险比（HR）= 0.41]。

Among patients with a detectable mutation at baseline (n = 104), early clearance (mutation undetectability) was observed in 47.1% at C1D15 and 52.4% at C2D1 and was associated with improved PFS (C1D15, HR = 0.51; C2D1, HR = 0.44).

在基线时检测到可检测突变的患者中（n = 104），在C1D15有47.1%的患者观察到早期清除（突变不可检测），在C2D1有52.4%的患者观察到早期清除，并且与改善的无进展生存期（PFS）相关（C1D15, HR = 0.51; C2D1, HR = 0.44）。

In patients without a detectable mutation at baseline, 22.7% (n = 34) developed new mutations at C1D15, C2D1, or first imaging.

在基线时未检测到突变的患者中，有22.7%（n = 34）在C1D15、C2D1或首次影像检查时发展出新的突变。

Patients without new mutations had a lower risk of progression (HR = 0.45).

没有新突变的患者进展风险较低（HR = 0.45）。

Conclusions

Pretreatment and early dynamics of ctDNA represent promising prognostic and predictive biomarkers in patients with HR+/HER2- ABC treated with ribociclib/letrozole.

在使用利奈西利布/来曲唑治疗的HR+/HER2- ABC患者中，治疗前和早期ctDNA动态是具有前景的预后和预测性生物标志物。

Early ctDNA dynamics seem to be a promising surrogate biomarker for treatment.

早期ctDNA动态似乎是治疗的一个有前景的替代性生物标志物。

Further studies are warranted to validate their clinical utility.

需要进一步的研究来验证其临床效用。