Peripheral Blood Biomarkers Associated with Clinical Outcome in Non-Small Cell Lung Cancer Patients Treated with Nivolumab

J Thorac Oncol. 2018 Jan;13(1):97-105. doi: 10.1016/j.jtho.2017.10.030. Epub 2017 Nov 21.

Abstract

Objective: The aim of this study was to identify baseline peripheral blood biomarkers associated with clinical outcome in patients with NSCLC treated with nivolumab.

Methods: Univariable and multivariable analyses were performed retrospectively for 134 patients with advanced or recurrent NSCLC treated with nivolumab to evaluate the relationship between survival and peripheral blood parameters measured before treatment initiation, including absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute monocyte count, and absolute eosinophil count (AEC), as well as serum C-reactive protein and lactate dehydrogenase levels. Progression-free survival, overall survival, and response rate were determined.

Results: Among the variables selected by univariable analysis, a low ANC, high ALC, and high AEC were significantly and independently associated with both better progression-free survival (p = 0.001, p = 0.04, and p = 0.02, respectively) and better overall survival (p = 0.03, p = 0.03, and p = 0.003, respectively) in multivariable analysis. Categorization of patients according to the number of favorable factors revealed that those with only one factor had a significantly worse outcome than those with two or three factors. A similar trend was apparent for patients with a programmed death 1 ligand tumor proportion score less than 50%, whereas all patients with a score of 50% or higher had at least two favorable factors.

Conclusions: A baseline signature of a low ANC, high ALC, and high AEC was associated with a better outcome of nivolumab treatment, with the number of favorable factors identifying subgroups of patients differing in survival and response rate.

Keywords: Nivolumab; Non–small cell lung cancer; Peripheral blood biomarker; Predictive factor; Prognostic factor.

MeSH terms

  • Adenocarcinoma / blood
  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / pathology
  • Aged
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / blood
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Carcinoma, Squamous Cell / blood
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / pathology
  • Female
  • Follow-Up Studies
  • Humans
  • Leukocytes / pathology*
  • Lung Neoplasms / blood
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / pathology*
  • Lymphocytes / pathology*
  • Male
  • Neutrophils / pathology*
  • Nivolumab
  • Prognosis
  • Retrospective Studies
  • Survival Rate

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Nivolumab