Associations between dynamic hematological indicators and outcomes in HR-positive, HER2-negative metastatic breast cancer treated with bireociclib or placebo plus fulvestrant: Findings from the BRIGHT-2 trial.

2025-12
Breast (Edinburgh, Scotland) 84
- Hangcheng Xu
- Yan Wang
- Qiang Sa
- Yiran Zhou
- Fei Ma
- Pin Zhang
- Ying Fan
- Ruigang Cai
- Qiao Li
- Bo Lan
- Jiani Wang
- Liang Cui
- Xinxin Tan
- Jing Bai
- Yan Hu
- Xianghui Duan
- Fan Yang
- Jiayu Wang
- Binghe Xu

PubMed: 41175808
DOI: 10.1016/j.breast.2025.104598

Study Design

Type: Randomized Controlled Trial (RCT)
Sample size: n = 305
Population: 305 patients with HR-positive, HER2-negative metastatic breast cancer from BRIGHT-2 trial
Methods: Post-hoc analysis of patients treated with bireocilib or placebo with fulvestrant; peripheral blood samples collected at baseline and on-treatment; survival assessed by Kaplan-Meier and Cox models
Funding: Unclear

Large Human Trial

Background

Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors combined with endocrine therapy have revolutionized the treatment landscape of hormone receptor (HR)-positive advanced breast cancer. However, reliable biomarkers for CDK4/6 inhibitors remain limited. This study investigated dynamic peripheral blood indicators as potential prognostic biomarkers for survival outcomes and therapeutic efficacy.

Methods

This post-hoc analysis included patients with HR-positive, HER2-negative metastatic breast cancer treated with bireocilib or placebo with fulvestrant from BRIGHT-2 trial. Peripheral blood samples collected at baseline and on-treatment were used to calculate absolute lymphocyte count (ALC), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII) and prognostic nutritional index (PNI). Kaplan-Meier analysis and Cox proportional hazards models assessed survival outcomes, while dynamic changes in indicators were compared using paired Wilcoxon signed-rank test.

Results

A total of 305 patients was included in this analysis. Bireociclib significantly improved PFS versus placebo regardless of MLR, PLR, and PNI levels (all p < 0.05). In multivariate Cox analysis, NLR, MLR, SII and PNI were independent prognostic factors for both PFS and overall survival (OS). None of the hematological indicators demonstrated significant predictive value across different treatment arms. In experimental group, PLR remained stable during treatment in the response group but increased significantly in the non-response group (p = 0.003). In control group, none of the indicators demonstrated significant changes from baseline to on-treatment point.

Conclusions

Peripheral blood-derived indicators are prognostic markers for HR-positive, HER2-negative metastatic breast cancer. Elevated PLR during treatment indicates poor response to CDK4/6 inhibitors.