Abstract P5-02-23: Association of Neutrophil-to-Lymphocyte Ratio and Absolute Lymphocyte Count with Clinical Outcomes for Patients with Advanced Breast Cancer in the MONARCH 2 Trial
Authors: Tokunaga Eriko , Miyoshi Yasuo , Dozono Koji , Kawaguchi Tsutomu , Toi Masakazu 
Published: March 2023

Abstract
Background: Pretreatment neutrophil-to-lymphocyte ratio (NLR) and absolute lymphocyte count (ALC) are putative prognostic factors in patients with advanced breast cancer (ABC). Little information is available on the prognostic value of these immune status markers in patients treated with abemaciclib (ABE). In this study, we investigated the relationship between baseline NLR and ALC and clinical outcomes using data from the phase 3 MONARCH 2 (M2) trial.
Methods: The M2 study compared ABE/fulvestrant to placebo (PBO)/fulvestrant in patients with estrogen-receptor positive, human epidermal growth factor receptor 2-negative ABC that had progressed on prior endocrine therapy. The current post hoc analyses used baseline laboratory data and outcome data from the June 20, 2019, cutoff date (median follow-up: 47.7 months). For both baseline NLR and baseline ALC, patients were divided into high and low categories, defined by a cutoff of 2.5 for NLR and 1.5 × 109/L for ALC. The association of baseline NLR and ALC with investigator-assessed progression-free survival (PFS) and overall survival (OS) was explored using Cox models stratified by treatment and described using Kaplan-Meier estimates. After assessing the prognostic value of baseline NLR and ALC for PFS and OS using a univariate analysis, a multivariate model was used to determine whether baseline NLR and ALC were independently prognostic considering additional baseline and disease characteristic factors.
Results: Data were available for 426 and 219 patients in the ABE and PBO arms, respectively. Median baseline NLR was 2.5 and 2.4 in the ABE and PBO arms, respectively. Median baseline ALC was 1.4 × 109/L in both arms. The numbers of patients categorized into the high and low categories were well balanced for analysis of both NLR and ALC.
Univariate analyses showed that baseline NLR (&lt; 2.5, ≥2.5) was a prognostic factor for PFS and OS (2-sided p&lt; 0.0001). Patients with low baseline NLR consistently had better PFS and OS than those with high baseline NLR, and the treatment effect of ABE against PBO was consistently observed regardless of NLR category (Table 1). Univariate analyses showed that baseline ALC (&lt; 1.5 × 109/L, ≥1.5 × 109/L) was also a prognostic factor for PFS and OS (2-sided p=0.0116 and 0.0032, respectively). PFS and OS were better for patients with high baseline ALC than for those with low baseline ALC, and the treatment effect of ABE against PBO was observed regardless of ALC category (Table 1).
For PFS, the multivariate model was adjusted for Eastern Cooperative Oncology Group performance status (ECOG PS), tumor grade, presence of liver metastasis, and bone-only disease. For OS, the multivariate model was adjusted for sensitivity to endocrine therapy, ECOG PS, presence of liver metastasis, and bone-only disease. When adjusting for these additional prognostic factors, baseline NLR, but not baseline ALC, remained statistically significant in the multivariate model (2-sided p&lt; 0.0001).
Conclusions: These exploratory analyses suggest that while both baseline NLR and ALC are prognostic of clinical outcomes, only baseline NLR is independently prognostic of PFS and OS. Low baseline NLR was associated with better PFS and OS outcomes, but the benefit of adding ABE to fulvestrant was similar regardless of baseline NLR status.
Table 1. Summary of outcomes by treatment arm for NLR and ALC categories ALC, absolute lymphocyte count; CI, confidence interval; NLR, neutrophil-to-lymphocyte ratio; NR, not reached; OS, overall survival; PFS, progression-free survival.
Citation Format: Eriko Tokunaga, Yasuo Miyoshi, Koji Dozono, Tsutomu Kawaguchi, Masakazu Toi. Association of Neutrophil-to-Lymphocyte Ratio and Absolute Lymphocyte Count with Clinical Outcomes for Patients with Advanced Breast Cancer in the MONARCH 2 Trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-02-23.