Neutrophil-to-Lymphocyte ratio (NLR) and Platelet-to-Lymphocyte ratio (PLR) as prognostic markers in patients with non-small cell lung cancer (NSCLC) treated with nivolumab

Lung Cancer. 2017 Sep;111:176-181. doi: 10.1016/j.lungcan.2017.07.024. Epub 2017 Jul 24.

Abstract

Objectives: Immunotherapy with the programmed death receptor-1 (PD-1) antibody nivolumab has changed the field of metastatic non-small cell lung cancer (NSCLC) treatment. Nivolumab shows better outcome compared to standard second line chemotherapy, but reliable prognostic markers are lacking. High neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are markers of host inflammation and associated with worse overall survival (OS) in several tumor types, but have not been analysed extensively in lung cancer in the era of immunotherapy.

Methods: Patients with metastatic NSCLC treated with nivolumab were enrolled. Pre-treatment NLR and PLR were calculated by division of neutrophils and platelets by lymphocytes measured in peripheral blood. Cox regression analyses were conducted to study the prognostic role of NLR and PLR on OS and progression free survival (PFS). Logistic regression was used to study the association of NLR and PLR. The combined impact of NLR and other known prognostic factors was explored with multivariable regression.

Results: Fifty-two patients were included. Elevated NLR was associated with worse OS (HR for log(NLR)=3.64, 95% CI 1.78-7.46, p<0.001) and lower response rates (OR for log(NLR)=0.17, 95% CI 0.04-0.68, p=0.013). There was no significant association with PFS (HR for log(NLR)=1.46, 95% CI=0.91-2.34, p=0.114). The AUC for the prediction of 10-month survival using log(NLR) was 0.738, the AUC for the prediction of response to nivolumab was 0.776. Relationships with PLR were similar. NLR and PLR didn't correlate with other known prognostic factors (i.e histology, tobacco use, ECOG performance status,) in our cohort. Inclusion of NLR in multivariable models with these other factors significantly improved the prediction of OS.

Conclusion: Elevated pre-treatment NLR and PLR are associated with shorter OS and PFS and with lower response rates in patients with metastatic NSCLC treated with nivolumab independently of other prognostic factors.

Keywords: Immunotherapy; Neutrophil-to-Lymphocyte ratio; Non small cell lung cancer; Overall survival; Platelet-to-Lymphocyte ratio.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Agents, Immunological / therapeutic use
  • Biomarkers
  • Carcinoma, Non-Small-Cell Lung / blood*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Female
  • Humans
  • Leukocyte Count*
  • Lung Neoplasms / blood*
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / mortality*
  • Lung Neoplasms / pathology
  • Lymphocyte Count*
  • Male
  • Middle Aged
  • Molecular Targeted Therapy
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Neutrophils*
  • Nivolumab
  • Platelet Count*
  • Prognosis
  • Retrospective Studies
  • Survival Analysis

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents, Immunological
  • Biomarkers
  • Nivolumab