P76.30 The Neutrophil-to-Lymphocyte Ratio is a Prognostic Biomarker in Patients with EGFR Mutated Advanced NSCLC

Abstract

An elevated neutrophil-to-lymphocyte ratio (NLR) indicates a poor prognosis across multiple cancers, including non-small cell lung cancer (NSCLC) and is associated with cancer cachexia. EGFR tyrosine kinase inhibitors (TKI) are typically associated with brisk responses and prolonged PFS benefit. This study evaluates baseline NLR and serial values in EGFR-mutated NSCLC patients receiving TKI therapy. Preliminary findings from a smaller cohort were submitted to ASCO 2020. We retrospectively analyzed 137 patients with advanced EGFR-mutated NSCLC treated with TKIs at Rush University Medical Center and University of Chicago Medical Center from August 2011 to July 2019. The prognostic value of NLR was assessed at the start of therapy, and after 6 and 12 weeks of treatment. Progression free survival (PFS) and overall survival (OS) were calculated by the Kaplan-Meier method and compared between groups with the log-rank test. Cox proportional hazards models were used to calculate the association between number of disease sites and survival outcomes. Spearman rank correlations were used to correlate number of disease sites with NLR at diagnosis. T-tests were used to compare mean NLR between patients with high or low grade toxicities. Changes in NLR and BMI were calculated by subtracting the value at treatment start from the values at 6 or 12 weeks, and the relationship between the change in NLR vs BMI were analyzed using Pearson correlation. At therapy start, patients with NLR <5 (n=88) had median PFS (mPFS) of 17.2 months and median OS (mOS) of 58.0 months, while those with NLR ≥5 (n=40) had mPFS of 14.0 months (p=0.0029) and mOS of 27.6 months (p=0.0024). After 6 weeks of treatment, patients with NLR <5 (n=104) had mPFS of 17.4 months and mOS of 59.7 months, while those with NLR ≥5 (n=27) had mPFS of 12.1 months (p=0.037) and mOS of 39.1 months (p=0.015). After 12 weeks of treatment, patients with NLR <5 (n=89) had mPFS of 18.4 months and mOS of 59.7 months, while those with NLR ≥5 (n=21) had mPFS of 5.8 months (p=0.0003) and mOS of 25.2 months (p=0.00083). There was a modest association between baseline number of disease sites and NLR at diagnosis (Spearman’s ρ=0.272, p=0.002), OS (HR=1.423, p<0.001), and PFS (HR=1.330, p<0.001). mPFS and mOS was not significantly different in patients whose NLR increased or decreased at 6 weeks (p=0.29) or 12 weeks (p=0.52). The change in BMI and change in NLR at 12 weeks was weakly correlated (r= -0.21, p=0.03), but changes in BMI did not correlate with OS (p=0.174) or PFS (p=0.439) at 12 weeks. There was no significant difference in NLR between patients with high grade (≥3) versus no or low grade (0-2) drug toxicities at 6 weeks (p=0.28) or 12 weeks (p=0.30), and development of grade 3-5 toxicities did not affect OS (p=0.8) or PFS (p=0.09). NLR is a prognostic factor which can predict which EGFR mutated NSCLC patients on TKIs may have worse PFS and OS. Potential therapeutic escalation may be beneficial in patients with elevated NLR≥5 on treatment and is worthy of study.