Abstract P2-03-03: Neutrophil-to-Lymphocyte Ratio (NLR) as a Potential Prognostic Marker in Patients with Hormone Receptor-Positive/HER2-Negative Advanced-Stage Breast Cancer Treated with CDK4/6 Inhibitors: A Focus on Ribociclib
Authors: Sharaf Baha’ , Qaddoumi Assem , Tamimi Faris , Abu-Fares Hala , Daoud Rand , Abdel-Razeq Hikmat 
Published: March 2023

Abstract
Background: Cyclin-dependent kinase (CDK) 4/6 inhibitors combined with endocrine therapies (ET) have become the mainstay treatment for patients with hormone receptor (HR)-positive, HER2-negative advanced-stage breast cancer. However, there is no established prognostic markers to predict its efficacy to better guide its utilization. Neutrophil-to-lymphocyte ratio (NLR), an indicator of the host systemic inflammatory/immune response, is widely studied marker in various settings in different cancer sites with variable but promising results. In this study, we evaluate the impact of NLR, as a prognostic biomarker, at baseline and prior to the third and fourth cycles of ET/ribociclib in patient with advanced-stage breast cancer. Methods: Data on consecutive patients with HR-positive/HER2−negative advanced-stage disease treated with ribociclib and an aromatase inhibitor or fulvestrant, were retrospectively reviewed from our institutional cancer registry and patients’ electronic medical records. NLR was calculated from blood counts performed at base line prior to commencing the first cycle of ribociclib, then prior to the third and fourth cycles, too, and was considered high if ≥ 2. Ribociclib was given at the usual dose and schedule; 600 mg daily for 3 weeks on and one week off. Progression-free survival (PFS) was defined as the time from the initiation of CDK4/6 inhibitor to the date of radiological or clinical progression or death. Multivariate analysis for PFS was performed using Cox’s proportional hazards regression model, covariates included age at diagnosis, ECOG performance status (≥ 1 vs. 0), body mass index (BMI) (≥ 25 vs. &lt; 25), ribociclib beyond first line vs. first line, type of ET (aromatase inhibitors vs. fulvestrant), visceral metastasis, postmenopausal vs. premenopausal, smoking status and de novo metastasis vs. recurrent disease and histopathology. Results: Between June 2017 and May 2020, a total of 257 patients were included, median age was 48 (22-87) years. Majority (n=163, 63.3%) received ribociclib as a first-line, 211 (82.4%) had invasive ductal carcinoma, 137 (53.3%) patients had de novo metastasis and 122 (47.7%) were premenopausal. Progression-free survival was significantly lower among patients with high NLR (n=143, 55.6%) at baseline; 17.8 vs. 22.9 months, P= 0.028. A similar trend for lower PFS was also noted for high NLR measured prior to the third (20.6 vs. 18.6 months) and the fourth cycles (21.6 vs. 18.2 months), however both were not statistically significant; P=0.154 and 0.09, respectively. Multivariate analysis confirmed an independent association between high NLR and lower PFS (adjusted HR 1.46, 95% CI 1.03-2.06, P= 0.032). Visceral metastasis (aHR 1.57, 95% CI 1.11-2.23, P=0.012) and receiving ribociclib beyond the first line (aHR 1.96, 95% CI 1.38-2.77, P&lt; 0.001, were also independent factors predicting inferior PFS. Conclusions: To the best of our knowledge this is the largest study to show a significant association between high NLR at baseline and lower PFS in patients with HR+ advanced-stage breast cancer treated with ribociclib and ET. If confirmed, NLR at base line may provide reliable, accessible, and widely available prognostic marker that can be used easily in routine clinical practice.
Citation Format: Baha’ Sharaf, Assem Qaddoumi, Faris Tamimi, Hala Abu-Fares, Rand Daoud, Hikmat Abdel-Razeq. Neutrophil-to-Lymphocyte Ratio (NLR) as a Potential Prognostic Marker in Patients with Hormone Receptor-Positive/HER2-Negative Advanced-Stage Breast Cancer Treated with CDK4/6 Inhibitors: A Focus on Ribociclib [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 P2-03-03.