The value of blood biomarkers of progression and prognosis in ALK-positive patients with non-small cell lung cancer treated with crizotinib

Asia Pac J Clin Oncol. 2020 Feb;16(1):63-69. doi: 10.1111/ajco.13284. Epub 2019 Nov 12.

Abstract

Aim: Valuable and convenient prognostic predictors are essential for targeted therapy of non-small cell lung cancer (NSCLC). Patients with early-stage cancer and EGFR mutations who's neutrophils-to-lymphocytes rate (NLR) could be prognostic factor to evaluate efficacy. However, the prognostic role of NLR in patients receiving ALK inhibitors has not been established. Additionally, the relation between the efficacy of ALK inhibitors and derived NLR (dNLR), platelets-to-lymphocytes rate (PLR), white blood cells (WBC) and hemoglobin (HGB) are still unknown.

Methods: This is a retrospective single-center study and enrolled 113 staged IIIB-IV ALK-positive NSCLC patients who had received crizotinib treatment. Pretreatment NLR, dNLR, PLR, WBC, HGB were collected and calculated. Cox regression analysis were conducted to study the prognostic roles of NLR, dNLR, PLR, WBC, and HGB on progression-free survival (PFS) and overall survival (OS). Z-test was utilized to identify the difference among all predictive factors' receiver-operating characteristics (ROC) curves.

Results: The median PFS and OS were 10.1 and 23.4 months. Elevated NLR, dNLR, PLR and decreased HGB were associated with worse PFS (95% confidence interval [CI], 1.078-2.304, P = 0.018; 95% CI, 1.043-2.222, P = 0.028; 95% CI, 1.257-2.757, P = 0.002; 95% CI, 0.368-0.843, P = 0.005, respectively) and OS (95% CI, 1.698-5.721, P < 0.001; 95% CI, 1.273-3.984, P = 0.005; 95% CI, 2.174-6.347, P < 0.001; 95% CI, 0.246-0.710, P = 0.001, respectively). Z-test revealed there were no significant differences between single factors or combination of them to predict the efficacy.

Conclusions: Trend of NLR, dNLR, PLR and WBC could be used to identify patients progress status in ALK-positive NSCLC patients receiving crizotinib. Combination of all biomarkers is no superior to single biomarker.

Keywords: anaplastic lymphoma kinase inhibitor; derived NLR; neutrophils-to-lymphocytes rate; non-small cell lung cancer; platelets-to-lymphocytes rate.

MeSH terms

  • Adenocarcinoma of Lung / blood
  • Adenocarcinoma of Lung / drug therapy
  • Adenocarcinoma of Lung / pathology
  • Anaplastic Lymphoma Kinase / metabolism*
  • Antineoplastic Agents / therapeutic use
  • Biomarkers / blood*
  • Blood Platelets / pathology*
  • Carcinoma, Non-Small-Cell Lung / blood
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Crizotinib / therapeutic use*
  • Disease Progression
  • Female
  • Humans
  • Lung Neoplasms / blood
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / pathology
  • Lymphocytes / pathology*
  • Male
  • Middle Aged
  • Neutrophils / pathology*
  • Prognosis
  • ROC Curve
  • Retrospective Studies
  • Survival Rate

Substances

  • Antineoplastic Agents
  • Biomarkers
  • Crizotinib
  • ALK protein, human
  • Anaplastic Lymphoma Kinase