Change in Neutrophil-to-lymphocyte Ratio in Response to Targeted Therapy for Metastatic Renal Cell Carcinoma as a Prognosticator and Biomarker of Efficacy

BACKGROUND - Neutrophil-to-lymphocyte ratio (NLR), if elevated, is associated with worse outcomes in several malignancies.

OBJECTIVE - Investigation of NLR at baseline and during therapy for metastatic renal cell carcinoma.

DESIGN, SETTING, AND PARTICIPANTS - Retrospective analysis of 1199 patients from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC cohort) and 4350 patients from 12 prospective randomized trials (validation cohort).

INTERVENTION - Targeted therapies for metastatic renal cell carcinoma.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS - NLR was examined at baseline and 6 (± 2) wk later. A landmark analysis at 8 wk was conducted to explore the prognostic value of relative NLR change on overall survival (OS), progression-free survival (PFS), and objective response rate using Cox or logistic regression models, adjusted for variables in IMDC score and NLR values at baseline.

RESULTS AND LIMITATIONS - Higher NLR at baseline was associated with shorter OS and PFS (Hazard Ratios [HR] per 1 unit increase in log-transformed NLR = 1.69 [95% confidence interval {CI} = 1.46-1.95] and 1.30 [95% CI = 1.15-1.48], respectively). Compared with no change (decrease < 25% to increase < 25%, reference), increase NLR at Week 6 by 25-50% and > 75% was associated with poor OS (HR=1.55 [95% CI=1.10-2.18] and 2.31 [95% CI=1.64-3.25], respectively), poor PFS (HR=1.46 [95% CI=1.04-2.03], 1.76 [95% CI=1.23-2.52], respectively), and reduced objective response rate (odds ratios = 0.77 [95% CI=0.37-1.63] and 0.24 [95% CI=0.08-0.72], respectively). By contrast, a decrease of 25-50% was associated with improved outcomes. Findings were confirmed in the validation cohort. The study is limited by its retrospective design.

CONCLUSIONS - Compared with no change, early decline of NLR is associated with favorable outcomes, whereas an increase is associated with worse outcomes.

PATIENT SUMMARY - We found that the proportion of immune cells in the blood is of prognostic value, namely that a decrease of the proportion of neutrophils-to-lymphocytes is associated with more favorable outcomes while an increase had the opposite effect.

European urology. 2016 Feb 25 [Epub ahead of print]

Arnoud J Templeton, Jennifer J Knox, Xun Lin, Ronit Simantov, Wanling Xie, Nicola Lawrence, Reuben Broom, André P Fay, Brian Rini, Frede Donskov, Georg A Bjarnason, Martin Smoragiewicz, Christian Kollmannsberger, Ravindran Kanesvaran, Nimira Alimohamed, Thomas Hermanns, J Connor Wells, Eitan Amir, Toni K Choueiri, Daniel Y C Heng

Princess Margaret Cancer Center, Division of Medical Oncology, Toronto, ON, Canada; Kantonsspital St. Gallen, Department of Medical Oncolgoy and Hematology, St. Gallen, Switzerland., Princess Margaret Cancer Center, Division of Medical Oncology, Toronto, ON, Canada., Pfizer Oncology, Pfizer Inc., New York, NY, USA., Pfizer Oncology, Pfizer Inc., New York, NY, USA., Dana Farber Cancer Institute, Biostatistics and Computational Biology, Boston, MA, USA., Auckland City Hospital, Auckland City Hospital, Grafton, Auckland, New Zealand., Auckland City Hospital, Auckland City Hospital, Grafton, Auckland, New Zealand., Dana Farber Cancer Institute, Biostatistics and Computational Biology, Boston, MA, USA., Cleveland Clinic Taussig Cancer Center, Cleveland, OH, USA., Aarhus University Hospital, Nørrebrogade, Aarhus, Denmark., Sunnybrook Odette Cancer Center, Toronto, ON, Canada., British Columbia Cancer Agency, Vancouver, BC, Canada., National Cancer Center Singapore, Singapore., Department of Medical Oncology, Tom Baker Cancer Center, Calgary, AB, Canada., Princess Margaret Cancer Center, Division of Medical Oncology, Toronto, ON, Canada; Department of Medical Oncology, Tom Baker Cancer Center, Calgary, AB, Canada., Princess Margaret Cancer Center, Division of Medical Oncology, Toronto, ON, Canada., Department of Medical Oncology, Tom Baker Cancer Center, Calgary, AB, Canada., Princess Margaret Cancer Center, Division of Medical Oncology, Toronto, ON, Canada., Dana Farber Cancer Institute, Biostatistics and Computational Biology, Boston, MA, USA., Department of Medical Oncology, Tom Baker Cancer Center, Calgary, AB, Canada.  

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