Predictive value of serum protein levels in patients with advanced non-small cell lung cancer treated with nivolumab. (June 2019)

• Record Type: Journal Article
• Authors: Oyanagi, Jun; Koh, Yasuhiro; Sato, Koichi; Mori, Keita; Teraoka, Shunsuke; Akamatsu, Hiroaki; Kanai, Kuninobu; Hayata, Atsushi; Tokudome, Nahomi; Akamatsu, Keiichiro; Nakanishi, Masanori; Ueda, Hiroki; Yamamoto, Nobuyuki
• Is Part Of: Lung cancer. Volume 132(2019)
• Page Start: 107
• Page End: 113
• Publication Date: 2019-06
• Subjects: Preclinical and translational research; PD-1 programmed cell death 1 -- PD-L1 programmed cell death-ligand 1 -- NSCLC non-small-cell lung cancer -- DCB durable clinical benefit -- PR partial response -- SD stable disease -- PD progressive disease -- irAE immune related adverse event -- TMB tumor mutational burden; Non-small-cell lung cancer -- Immune checkpoint inhibitors -- Noninvasive diagnostics -- Immune related adverse events -- Serum biomarker; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2019.03.020
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: Serum cytokines and growth factors were assessed during nivolumab treatment. Follistatin and IP-10 levels are associated with durable clinical benefit. Levels of serum RANTES are associated with irAE onset. Clinical benefit and irAEs are regulated by different immune mechanisms. Abstract: Background: Although programmed cell death-ligand-1 (PD-L1) expression in tumor tissue has been established as predictive biomarker for the anti-programmed cell death-1 (PD-1) antibody treatment of non-small-cell lung cancer (NSCLC), additional biomarkers are critically needed. We evaluated serum proteins relevant to immune checkpoint blockade in patients with NSCLC treated with nivolumab to identify novel non-invasive predictive biomarkers. Patients and methods: Patients with advanced NSCLC, who had failed at least one prior chemotherapy regimen, received nivolumab monotherapy (3 mg/kg, Q2W) until progressive disease (PD) or unacceptable toxicity was observed. Blood samples were collected at baseline and week 4. Fifty-seven serum protein levels were quantified with a Milliplex MAP assay. The associations of both clinical benefit (CB) and the onset of immune related adverse events (irAEs) with serum proteins levels were evaluated. Results: Thirty-eight patients with advanced NSCLC were enrolled in the study, with 38 and 32 paired serum samples at baseline and week 4 being available for efficacy analysis and irAE analysis, respectively. In durable CB (DCB) patients compared with non-DCB patients, the baseline serum levels of BMP-9 were significantly higher, whereas the follistatin, IL-8, IP-10, and TNF-α levels were significantly lower. In irAE patients compared with non-irAE patients the serum levels of G-CSF and RANTES at week 4 were significantly higher, whereas the levels of leptin were significantly lower. A multivariate analysis revealed that follistatin and IP-10 were statistically associated with DCB (p < 0.05) and RANTES was associated with irAE onset (p < 0.05). In a subset of irAE-developed patients, RANTES levels decreased after steroid administration, supporting its involvement in irAE. Conclusion: Serum proteins have the potential to be predictive markers for DCB and irAEs onset in patients with NSCLC treated with nivolumab. In addition, antitumor activity and irAEs may not be regulated by the same mechanisms.