Circulating Tumor Cell Dynamics after CDK4/6 Inhibitor for Hormone Receptor-Positive Metastatic Breast Cancer: A Biomarker Analysis from the PACE Phase II Study.

This analysis evaluates the prognostic role of baseline CTC enumeration and its interaction with treatment regimens in patients progressing on CDK4/6 inhibitors.

本分析评估了基线CTC计数的预后作用及其与CDK4/6抑制剂治疗方案的相互作用，研究对象为接受CDK4/6抑制剂治疗后进展的患者。

experimental_design

The PACE trial is a phase II, multicenter, randomized study of patients with HR+/HER2- MBC experiencing progression on aromatase inhibitors and CDK4/6 inhibitors.

PACE试验是一项II期、多中心、随机研究，针对接受芳香酶抑制剂和CDK4/6抑制剂治疗后进展的HR+/HER2- MBC患者。

Patients were randomized 1:2:1 to receive fulvestrant (F), F + palbociclib (F + P), or F + P + avelumab (F + P + A).

患者按1:2:1的比例随机接受氟维司群(F)、F + 帕博西利(F + P)或F + P + 阿维鲁单抗(F + P + A)治疗。

Baseline CTCs were enumerated using CellSearch with a threshold of ≥5 CTCs/7.5 mL to classify patients as stage IVindolent or stage IVaggressive.

使用CellSearch对基线循环肿瘤细胞(CTCs)进行计数，以≥5 CTCs/7.5 mL为阈值，将患者分类为IV期惰性或IV期侵袭性。

Concurrent ctDNA analysis was performed using Guardant360.

同时使用Guardant360进行了循环肿瘤DNA(ctDNA)分析。

Progression-free survival(PFS) was the primary endpoint.

无进展生存期（PFS）是主要终点。

Results

Among 220 randomly assigned patients, 203 were evaluable for baseline CTCs; 76% had detectable CTCs and 49% were stage IVaggressive.

在220名随机分配的患者中，203名患者可用于基线CTCs的评估；76%的患者检测到CTCs，49%为IV期侵袭性。

Patients with de novo MBC were more frequently stage IVaggressive (47.5% vs. 30.8%).

初发性转移性乳腺癌患者中，IV期侵袭性病例更为常见（47.5%对比30.8%）。

Baseline CTCs were prognostic with median PFS of 5.7 months for stage IVindolent and 3.5 months for stage IVaggressive patients [HR = 1.69; 90% confidence interval(CI), 1.27-2.24; P < 0.001].

基线循环肿瘤细胞（CTCs）具有预后意义，IV期惰性患者的中位无进展生存期为5.7个月，而IV期侵袭性患者的中位无进展生存期为3.5个月 [风险比（HR）= 1.69; 90%置信区间（CI），1.27-2.24; P < 0.001]。

In stage IVaggressive patients, F + P and F + P + A improved PFS versus fulvestrant alone (HR = 0.43; 90% CI, 0.25-0.71 and HR = 0.26; 90% CI, 0.14-0.49, respectively).

在IV期侵袭性患者中，F + P和F + P + A与fulvestrant单药治疗相比，改善了无进展生存期（PFS），风险比（HR）分别为0.43（90%置信区间，0.25-0.71）和0.26（90%置信区间，0.14-0.49）。

No benefit was observed in stage IVindolent patients (interaction P = 0.0148 and P = 0.0033, respectively).

在IV期惰性患者中未观察到任何益处（交互作用P值分别为0.0148和0.0033）。

Conclusions

Baseline CTC enumeration provides significant prognostic information in HR+/HER2- MBC.

基线循环肿瘤细胞(CTC)计数在HR+/HER2-转移性乳腺癌(MBC)中提供了显著的预后信息。

Stage IVaggressive patients derive greater benefit from F + P or F + P + A over fulvestrant alone, independent of clinical or ctDNA features.

IV期侵袭性患者从F + P或F + P + A治疗中获得的益处大于仅用fulvestrant治疗，这与临床特征或ctDNA特征无关。

This highlights the potential of CTCs to guide treatment decision-making.

这突显了循环肿瘤细胞（CTCs）在指导治疗决策方面的潜力。