Prognostic Implications of Neutrophil to Lymphocyte Ratio in the Treatment of Metastatic Renal Cell Carcinoma with Pazopanib and Sunitinib Ajay Raghunath1, Milo Murphy1, Karen Zhang1, Phillip Parente1,2, Joseph McKendrick1,2, Ian Davis1,2, Carmel Pezaro1,2 1 Eastern Health Clinical School, Box Hill, Victoria, 2 Eastern Health, Box Hill, Victoria Background Renal cell carcinoma contributes to 2-3% of cancers worldwide. Improved stratification of patients will assist clinicians in selecting appropriate management strategies.1 Neutrophil to lymphocyte ratio (NLR) is an independent prognostic factor in metastatic clear cell renal cell carcinoma (ccRCC).2 NLR greater than 3 has been suggested as a predictive marker for first-line tyrosine kinase inhibitor (TKI) therapy, however the associations of NLR in patients receiving specific TKIs, particularly sunitinib or pazopanib, have not been clearly established.3 We therefore aimed to explore NLR in metastatic ccRCC patients treated with sunitinib or pazopanib. Methods We retrospectively examined patients with metastatic ccRCC treated at Eastern Health, under an ethically approved protocol. Patients identified by pharmacy records were divided into two groups based on initial targeted therapy (sunitinib vs. pazopanib). NLR was calculated at the initiation of treatment and after 6 weeks. The primary outcome measure was overall survival (OS) from initiation of therapy. Kaplan-Meier survival analysis was used to calculate median OS. Cox regression was used to assess the prognostic role of NLR conversion in both treatment groups. All statistical analyses were performed using SPSS v.22 (SPSS, Chicago, Illinois). Results We included a total of 59 patients, 37 of whom were initially treated with sunitinib, while 22 were treated with pazopanib. In the entire cohort, baseline NLR>3 was associated with a reduced median OS (9.7 vs. 36.3 months if NLR <3, HR 2.45, p=0.03). There was a trend towards worse survival with pazopanib treatment in patients with baseline NLR>3 (HR 4.1, p=0.08) that was less apparent with sunitinib (HR 1.75, p=0.26). Reduction in NLR after six weeks of TKI therapy showed a non-statistic trend to improved survival with both sunitinib (13.2 if NLR converted to <3 vs. 3.3 months if NLR remained >3, p=0.52) and pazopanib (10.5 vs. 4.0 months, p=0.23). However, the analysis was limited by the small number of events. Survival in Neutrophil to Lymphocyte Ratio Cohorts Baseline Characteristics Characteristic Full Cohort (n=59) Sunitinib (n=37) Pazopanib (n=22) Age at TKI – years (y; range) 67.9 (33-87) 68.0 (33-82) 67.5 (35-87) Age at diagnosis – y (range) 58.8 (32-87) 60.4 (32-82) 55.0 (34-87) Male (%) 41/59 (69.5) 22/37 (59.5) 19/22 (86.4) Nephrectomy (%) 46/59 (78.0) 26/37 (70.3) 20/22 (90.9) IMDC Prognostic Score (%) Poor Intermediate Favourable Missing Data 21/59 (35.6) 9/59 (15.3) 16/59 (27.1) 13/59 (22.0) 13/37 (35.1) 4/37 (10.8) 9/37 (24.3) 11/37 (29.7) 8/22 (36.4) 5/22 (22.7) 7/22 (31.8) 2/22 (9.0) Overall Survival From Initiation of Therapy Conclusion Baseline NLR>3 was associated with poorer prognosis in our metastatic ccRCC cohort overall and potentially in patients receiving pazopanib. A reduction in NLR at six weeks may be associated with improved outcome on TKI therapy, regardless of type. Validation with a larger database is planned to further investigate the relationship between NLR and specific first-line TKI therapy. Sunitinib Pazopanib References 1. Rini BI, Campbell SC, Escudier B. Renal cell carcinoma. Lancet. 2009;373(9669):1119-32. 2. Hu K, Lou L, Ye J, Zhang S. Prognostic role of the neutrophil-lymphocyte ratio in renal cell carcinoma: a meta-analysis. BMJ Open. 2015;5(4):e006404. Park YH, Ku JH, Kwak C, Kim HH. Post-treatment neutrophil-to-lymphocyte ratio in predicting prognosis in patients with metastatic clear cell renal cell carcinoma receiving sunitinib as first line therapy. Springerplus. 2014;3:243. IDD is supported by an NHMRC Practitioner Fellowship (APP1102604)