Abstract A057: Serial evaluation of multiple serum protein levels in non-small lung cancer patients treated with nivolumab
Authors: Oyanagi Jun , Koh Yasuhiro , Akamatsu Hiroaki , Kanai Kuninobu , Hayata Atsushi , Tokudome Nahomi , Akamatsu keiichiro , Nakanishi Masanori , Ueda Hiroki , Yamamoto Nobuyuki 
Published: August 2018

Abstract
Background: Blockade of programmed death receptor-1 (PD-1) pathway is effective against various malignancies. Although PD-ligand 1 (PD-L1) expression on tumor tissue has been established as companion diagnostics in non-small cell lung cancer (NSCLC), additional biomarkers to enrich the patients likely to benefit from the therapy are critically needed. Here, we conducted a serial evaluation of multiple serum cytokines, growth factors, and angiogenesis factors relevant to immune checkpoint blockade in NSCLC patients treated with nivolumab. Patients and Methods: Advanced NSCLC patients after failure of at least one prior chemotherapy regimen received nivolumab monotherapy (3mg/kg, q2W) until progressive disease (PD) or unacceptable toxicity. Serum samples were collected in a serum separation tube (Venoject II autosep, TERUMO) at baseline and at week 4. Best response was classified into partial response (PR), stable disease (SD), or progressive disease (PD) according to RECIST v1.1. Using LuminexTM xMapTM technology, serum levels of 54 proteins consisting of cytokines, chemokines, growth factors, and angiogenesis factors were analyzed. All statistical analyses were carried out using JMP Pro software (ver. 13.0) and Mann-Whitney U test and Spearman's test were performed accordingly. A p value &lt;0.05 was considered as significant. Results: Thirty-eight patients were registered in the study between January 2016 and March 2017 at Wakayama Medical University Hospital and 34 were included in the analysis. Demographics of the patients were as follows: median age 68 (range, 49 to 86); male 73 %; stage IV, 100%; squamous/non-squamous, 30/70 %. Overall response rate was 22% (7/34), and disease control rate was 53% (18/34). Among 54 serum proteins measured serially, the levels of serum IL-8 and TNF-α were significantly lower at baseline in non-PD patients than in PD patients (p &lt; 0.01 in both cases). In addition, the levels of both serum IL-8 and TNF-α were correlated with longer progression-free survival (PFS) (r=-0.4695 and -0.5912, respectively). It is noteworthy that serum IL-8 levels at week 4 in PR patients were significantly lower than those in non-PR patients (p &lt;0.01). Correlation between IL-8 levels at week 4 and longer PFS was shown to be more significant (r=-0.6864). Serum VEGF-A levels were significantly lower in PR patients than those in non-PR patients at week 4 (p &lt;0.05). Conclusions: We identified the serum levels of IL-8, TNF-α, and VEGF-A as potential biomarkers to predict clinical benefit from nivolumab treatment in advanced NSCLC by multi-analyte protein-based assay. Incorporating serum TNF-α levels may have potential to improve the patient enrichment in addition to previously reported potential biomarkers such as IL-8 and VEGF levels. Further evaluation is warranted in a larger cohort to validate the findings.
Citation Format: Jun Oyanagi, Yasuhiro Koh, Hiroaki Akamatsu, Kuninobu Kanai, Atsushi Hayata, Nahomi Tokudome, keiichiro Akamatsu, Masanori Nakanishi, Hiroki Ueda, Nobuyuki Yamamoto. Serial evaluation of multiple serum protein levels in non-small lung cancer patients treated with nivolumab [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A057.