Dynamic hematological indicators as predictors of CDK4/6 inhibitors efficacy in HR-positive, HER2-negative metastatic breast cancer.

Abstract

e13075 Background: Birociclib, a novel CDK4/6 inhibitor, has been evaluated in the BRIGHT-2 study, a phase 3 randomized controlled trial (RCT), to assess its efficacy and safety when combined with fulvestrant versus placebo plus fulvestrant in the treatment of HR+/HER2- advanced breast cancer that progressed during or after prior endocrine therapy (NCT05077449). The study demonstrated that birociclib combined with fulvestrant significantly improved progression-free survival (PFS) compared to the control group. Despite these promising results, reliable predictive biomarkers for birociclib efficacy remain limited. This study investigates the potential of dynamic hematological indicators as predictive biomarkers for the efficacy of CDK4/6 inhibitors. Methods: This exploratory analysis of the BRIGHT-2 trial included patients with HR-positive, HER2-negative metastatic breast cancer treated with birociclib plus fulvestrant. Peripheral blood samples collected at baseline and on-treatment (day 1, cycle 5) 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). Cut-off values were determined using ROC curve analysis and the Youden Index. Kaplan-Meier analysis and Cox proportional hazards models assessed survival outcomes including progression-free survival (PFS) and overall survival (OS), while dynamic changes in indicators were compared using paired t-tests. Results: Among 204 patients, higher baseline ALC and PNI were associated with longer PFS and OS, whereas higher NLR, MLR, PLR, and SII predicted worse outcomes. PNI was independently prognostic for PFS, while NLR, MLR, PLR, and SII independently predicted OS. During treatment, ALC, NLR, MLR, SII, and PNI significantly decreased in both response and non-response groups (all p < 0.001). PLR remained stable in the response group but increased significantly in the non-response group (p = 0.003). Conclusions: Peripheral blood-derived indicators, including ALC, NLR, MLR, PLR, SII, and PNI, are predictive of CDK4/6 inhibitor efficacy in HR-positive, HER2-negative metastatic breast cancer. Elevated PLR during treatment indicates poor response to CDK4/6 inhibitors. Clinical trial information: NCT05077449 .