Neutrophil-to-Lymphocyte Ratio Is a Predictive Biomarker in Patients with Epidermal Growth Factor Receptor (EGFR) Mutated Advanced Non-Small Cell Lung Cancer (NSCLC) Treated with Tyrosine Kinase Inhibitor (TKI) Therapy

SIMPLE SUMMARY: Though patients with sensitizing epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer have been known to have rapid and durable responses to tyrosine kinase inhibitors, a subset of patients have inferior outcomes and may benefit from therapy escalation. Neutrophil-to-lymphocyte ratio (NLR) has been recognized as one indicator of poor prognosis in patients with various cancers, including non-small cell lung cancer. It is associated with cancer cachexia and treatment resistance. The aim of our study is to assess the serial predictive value of NLR and other markers of cachexia and chronic inflammation in the subset of patients with advanced non-small cell lung cancer who harbor the epidermal growth factor receptor mutation and who are undergoing treatment with tyrosine kinase inhibitor therapy. ABSTRACT: Background: First-line treatment for patients with non-small cell lung cancer (NSCLC) with a sensitizing epidermal growth factor receptor (EGFR) mutation is a tyrosine kinase inhibitor (TKI). Despite higher response rates and prolonged progression free survival (PFS) compared with platinum doublet chemotherapy, a subset of these patients do not receive prolonged benefit from these agents. We investigate if the neutrophil-to-lymphocyte ratio (NLR) and other markers of cachexia and chronic inflammation correlate with worse outcomes in these patients. Methods: This study is a retrospective review of 137 patients with advanced EGFR-mutated NSCLC treated with TKIs at Rush University Medical Center and University of Chicago Medicine from August 2011 to July 2019, with outcomes followed through July 2020. The predictive value of NLR and body mass index (BMI) was assessed at the start of therapy, and after 6 and 12 weeks of treatment by univariable and multivariable analyses. Results: On univariable analysis, NLR ≥ 5 or higher NLR on a continuous scale were both associated with significantly worse PFS and overall survival (OS) at treatment initiation, and after 6 or 12 weeks of treatment. On multivariable analysis, NLR ≥ 5 was associated with increased risk of death at 12 weeks of therapy (HR 3.002, 95% CI 1.282–7.029, p = 0.011), as was higher NLR on a continuous scale (HR 1.231, 95% CI 1.063–1.425, p = 0.0054). There was no difference in PFS and OS and amongst BMI categories though number of disease sites and Eastern Cooperative Oncology Group (ECOG) performance status was associated with worse PFS and OS. Conclusions: Patients with NLR ≥ 5 have a worse median PFS and median OS than patients with NLR < 5. NLR may have value as a predictive biomarker and may be useful for selecting patients for therapy intensification in the front-line setting either at diagnosis or after 12 weeks on therapy. NLR needs to be validated prospectively.