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

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.

Platelet‑to‑lymphocyte and neutrophil‑to‑lymphocyte ratios are associated with the efficacy of immunotherapy in stage III/IV non‑small cell lung cancer

“…In contrast to a previous study (35), the present univariate analysis suggested that number of metastases and mutation status were associated with PFS and OS estimates. In clinical practice, patients with multiple metastases tend to be in poor overall health, have advanced disease and poor previous treatment response, as well as high toxicity susceptibility.…”

“…Circulating neutrophils promote tumor growth and metastasis through tumor inflammatory mediators (arginine and nitric oxide). NLR values have been shown to have prognostic relevance in various types of cancer, including NSCLC ( 35), esophageal cancer (32) and pelvic malignancies (36). In the present study, higher NLR values were associated with poorer PFS (mPFS, 5.73 vs. 9.17 months) and OS (mOS, 12.03 vs. 26.33 months) in the H-NLR group compared with in the L-NLR group.…”

Systemic Inflammation Index and Tumor Glycolytic Heterogeneity Help Risk Stratify Patients with Advanced Epidermal Growth Factor Receptor-Mutated Lung Adenocarcinoma Treated with Tyrosine Kinase Inhibitor Therapy

“…It promotes tumor-promoting activities, including angiogenesis, mutagenesis, and immunosuppression [ 10 ]. Hematological parameters, such as the neutrophil-to-lymphocyte ratio (NLR) and systemic inflammation index (SII), have prognostic roles in various malignancies, including lung cancer, as potential cancer inflammation-induced biomarkers [ 11 , 12 , 13 , 14 , 15 , 16 ]. These peripheral blood parameters are of notable interest because of their easy and ready accessibility in clinical practice [ 17 ].…”

Prognostic Values of Inflammatory Indexes and Clinical Factors in Patients with Epidermal Growth Factor Receptor Mutations in Lung Adenocarcinoma and Treated with Tyrosine Kinase Inhibitors

“…Extensive research has previously revealed that blood-based inflammatory/immune markers, including lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) are significant prognostic indicators of NSCLC [ 12 , 13 , 14 , 15 ]. These hematological markers can be detected inexpensively and conveniently in clinical practice and could possibly reflect tumor-promoting activities [ 16 ].…”