Abstract P3-08-49: Baseline neutrophil-to-lymphocyte ratio and C-reactive protein predict efficacy of bevacizumab plus paclitaxel therapy for locally advanced or metastatic breast cancer
Authors: Ozawa Hiromi , Miyagawa Yoshimasa , Yanai Ayako , Yanagawa Takehiro , Inatome Jyunichi , Egawa Chiyomi , Nishimukai Arisa , Takamoto Kaori , Morimoto Takashi , Sata Atsushi , Fukui Reiko , Bun Ayako , Higuchi Tomoko , Fujimoto Yukie , Imamura Michiko , Miyoshi Yasuo 
Published: March 2020

Abstract
Background Vascular endothelial growth factor (VEGF) is a key player in angiogenesis, and bevacizumab, a humanized monoclonal antibody against VEGF-A, is already utilized in daily clinical practice coupled with chemotherapy for locally advanced and metastatic breast cancers (ABC). Although the impact of bevacizumab plus paclitaxel therapy on PFS was prominent, no OS benefit has been demonstrated so far. Identification of a robust biomarker for bevacizumab therapy in terms of benefit on OS is a critical issue. Since VEGF modulates various functions of cancer immunity, direct inhibition of VEGF, in addition to vascular normalization by bevacizumab may lead to improvement of immune microenvironment, resulting in favorable prognosis in patients. On the basis of this aspect, predictive efficacy of peripheral immune related parameters were investigated in patients treated with bevacizumab plus paclitaxel. Method A total of 182 patients with locally advanced and metastatic breast cancers treated with bevacizumab plus paclitaxel were retrospectively recruited from three institutes. We measured neutrophil-to-lymphocyte ratio (NLR), absolute lymphocyte count (ALC), and c-reactive protein (CRP) in the peripheral blood taken at baseline (the same day just before start of 1st treatment). Bevacizumab 10 mg/kg on days 1 and 15 and paclitaxel 80 or 90 mg/m2 on day 1, 8, and 15 of each 28-day cycle were administered intravenously. The cut-off values of NLR, ALC, and CRP were set at 3, 1500/μL, and 1.0mg/dL, respectively and baseline values of these factors were measured. Results We divided the patients into NLR-high (n=101) and -low (n=81); CRP-high (n=62) and -low (n=89). The progression-free survival (PFS) of patients with NLR-low was significantly longer than that of patients with NLR-high (median, 12.6 vs. 7.2 months; hazard ratio (HR), 0.47; 95% confidence interval (CI), 0.31-0.70; p=0.0002). In addition, OS of patients with NLR-low was significantly better than those with -high (22.2 vs. 13.5 months; HR, 0.55; 95% CI, 0.38-0.80; p=0.0017). Similarly, improved PFS and OS were recognized in patients with CRP-low as compared with -high (HR, 0.42; 95% CI, 0.27-0.66; p&lt;0.0001 and HR, 0.38; 95% CI, 0.25-0.59; p&lt;0.0001, respectively). By multivariable analysis, both NLR-low (HR, 0.56; 95% CI, 0.33-0.91; p=0.0198) and CRP-low (HR, 0.50; 0.32-0.79; p=0.003) were significantly and independently associated with longer PFS. As for OS, both NLR (HR, 0.61; 95% CI, 0.38-0.97; p=0.0368) and CRP (HR, 0.39; 95% CI, 0.24-0.63; p=0.0001) were significant and independent predictors by multivariable analysis.Discussion and conclusion Low levels of NLR and CRP at baseline were found to be significantly associated with improved PFS as well as OS in patients treated with bevacizumab plus paclitaxel. Although the detailed mechanisms are currently unknown, patients with low NLR or CRP at baseline may represent a favorable immune microenvironment which could be linked with an increased treatment efficacy. NLR and CRP levels at baseline seem to be useful for selecting patients who could benefit in terms of OS from bevacizumab treatment.
Citation Format: Hiromi Ozawa, Yoshimasa Miyagawa, Ayako Yanai, Takehiro Yanagawa, Jyunichi Inatome, Chiyomi Egawa, Arisa Nishimukai, Kaori Takamoto, Takashi Morimoto, Atsushi Sata, Reiko Fukui, Ayako Bun, Tomoko Higuchi, Yukie Fujimoto, Michiko Imamura, Yasuo Miyoshi. Baseline neutrophil-to-lymphocyte ratio and C-reactive protein predict efficacy of bevacizumab plus paclitaxel therapy for locally advanced or metastatic breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-49.