Baseline serum levels of osteopontin predict clinical response to treatment with nivolumab in patients with non-small cell lung cancer

Clin Exp Metastasis. 2019 Oct;36(5):449-456. doi: 10.1007/s10585-019-09984-z. Epub 2019 Aug 2.

Abstract

Treatment with nivolumab improves survival and response rate in non-small cell lung cancer (NSCLC). Nevertheless, due to its high financial cost, identifying predictors of response to treatment has become an urgent need. Here, we focused on serum osteopontin (OPN), a pleiotropic protein overexpressed in lung cancer and involved in the immune response. A cohort of NSCLC patients (n = 72) treated with nivolumab was enrolled. Blood samples were collected at the time of first five nivolumab administrations. OPN and high-sensitivity C-reactive protein (hs-CRP) were assayed at each time point. The primary endpoint was to assess the predictive value of baseline serum levels of OPN towards overall survival (OS). Secondary endpoints included the potential association between OPN, hs-CRP and response to nivolumab. OPN and hs-CRP correlate with each other, with neutrophil count and biochemical markers of metastatic disease. At baseline, serum OPN increased with increasing Eastern Cooperative Oncology Group scale of Performance Status (ECOG PS). When Eastern Cooperative Oncology Group scale of Performance Status) (RECIST) criteria were considered, high baseline OPN levels were associated with a worse response to nivolumab. Cox hazard regression further confirmed baseline serum OPN as a predictor of mortality with the best predictive accuracy for serum levels above 37.7 ng/mL. Patients above the cut-off value had a higher mortality rate as compared to low serum OPN levels during follow up. Serum OPN may have a predictive role in NSCLC patients treated with nivolumab. Although larger confirmatory studies are needed, measuring serum OPN levels at baseline can be a clinically useful tool in a near future.

Keywords: Inflammation; Neutrophil; Nivolumab; Non-small cell lung cancer; Osteopontin.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Biomarkers, Tumor / blood*
  • C-Reactive Protein / analysis*
  • Carcinoma, Non-Small-Cell Lung / blood
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Lung Neoplasms / blood
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / pathology*
  • Male
  • Nivolumab / therapeutic use*
  • Osteopontin / blood*
  • Pilot Projects
  • Prognosis
  • Severity of Illness Index
  • Survival Rate

Substances

  • Antineoplastic Agents, Immunological
  • Biomarkers, Tumor
  • SPP1 protein, human
  • Osteopontin
  • Nivolumab
  • C-Reactive Protein