Pretreatment neutrophil to lymphocyte ratio as prognostic factor in metastatic breast cancer treated with cyclin dependent kinase 4/6 inhibitors

Abstract Background: Cyclin dependent kinase inhibitors (CdK4/6i) changed the course of hormone receptor positive (HR+) HER2negative (HER2-) metastatic breast cancer (mBC). To date, no factors have been shown to predict response to CdK4/6i. Neutrophil-to-lymphocyte ratio (NLR), an indicator of the host systemic inflammatory response, is an independent prognostic factor for survival in cancers. We conducted this study to evaluate the addition of NLR for survival assessment in mBC patients treated with first line CdK4/6i. Methods: All mBC patients treated with first line CdK4/6i between November 2015 and December 2019 were retrospectively included. We analyzed 12-month progression free survival (PFS), overall survival (OS) and response rate according to NLR in univariable and multivariable analysis.Results: A total of 126 patients treated with palbociclib (n=101), ribociclib (n=18) or abemaciclib (n=7) were included, with a median follow-up of 16 months [range: 2.9-37]. Median age was 65 years [29-86], 88% patients had good performance status (0-1). Most patients were included at the metastatic relapse stage (71%) and 20% had visceral metastases without bone lesions. High NLR (≥ 2.53) was significantly associated with worse PFS (Hazard Ratio (HR)=0.52, CI95% =[0.29-0.94]). Fourteen patients died (11.1%). Complete responses were more frequent in the low NLR group (<2.53) (14.5% vs. 3.1%, p=0.029). Conclusion: High NLR is associated with worse PFS in HR+ HER2- mBC patients treated with first line CdK4/6i. NLR is a reliable and inexpensive prognostic marker, easily accessible in routine clinical practice, which could optimize the therapeutic strategy. These results need to be confirmed in larger prospective studies.