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

Federico Carbone, Francesco Grossi, Aldo Bonaventura, Alessandra Vecchié, Silvia Minetti, Nicholas Bardi, Edoardo Elia, Anna Maria Ansaldo, Daniele Ferrara, Erika Rijavec, Maria Giovanna Dal Bello, Federica Biello, Giovanni Rossi, Marco Tagliamento, Angela Alama, Simona Coco, Paolo Spallarossa, Franco Dallegri, Carlo Genova, Fabrizio Montecucco

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)449-456
Number of pages8
JournalClinical and Experimental Metastasis
Issue number5
Publication statusPublished - Oct 15 2019


  • Inflammation
  • Neutrophil
  • Nivolumab
  • Non-small cell lung cancer
  • Osteopontin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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