Association of Neutrophil-to-Lymphocyte Ratio and Absolute Lymphocyte Count With Clinical Outcomes in Advanced Breast Cancer in the MONARCH 2 Trial.

Abstract

Established prognostic factors for treatment response to cyclin-dependent kinases 4 and 6 inhibitors are currently lacking. We aimed to investigate the relationship of pretreatment neutrophil-to-lymphocyte ratio (NLR) and absolute lymphocyte count (ALC) to abemaciclib outcomes. This was a post hoc analysis of data from MONARCH 2, a phase III study of abemaciclib or placebo plus fulvestrant in hormone-receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer that progressed on endocrine therapy. Patients were divided into high and low categories based on baseline NLR (cutoff: 2.5) and ALC (cutoff: 1.5 × 109/L). The association of baseline NLR and ALC with progression-free survival (PFS) and overall survival (OS) was explored using Cox models and Kaplan-Meier estimates. Tumor response and safety were also examined. NLR and ALC data were available for 645 patients (abemaciclib: N = 426; placebo: N = 219). Low-baseline NLR or high-baseline ALC was consistently associated with positive PFS and OS trends; low-baseline NLR subgroups also showed trends for better response. The abemaciclib treatment effect against placebo was observed regardless of baseline NLR or ALC. Univariate analyses showed baseline NLR and ALC were prognostic of PFS and OS. Baseline NLR remained significant in the multivariate model (P < .0001). No unexpected differences in safety were observed by baseline NLR or ALC. Baseline NLR was independently prognostic of PFS and OS. Low-baseline NLR was associated with numerically better efficacy outcomes, but the benefit of adding abemaciclib to fulvestrant was similar irrespective of baseline NLR status.