Soluble programmed cell death ligand 1 predicts prognosis for gastric cancer patients treated with nivolumab: Blood-based biomarker analysis for the DELIVER trial

Eur J Cancer. 2023 May:184:10-20. doi: 10.1016/j.ejca.2023.02.003. Epub 2023 Feb 10.


Background: The clinical value of soluble forms of programmed cell death-1 (sPD-1), PD ligand 1 (sPD-L1) and cytotoxic T lymphocyte-associated protein-4 (sCTLA-4) for gastric cancer (GC) patients treated with nivolumab monotherapy has remained unknown.

Methods: Blood samples collected before nivolumab treatment from 439 GC patients enrolled in the DELIVER (Japan Clinical Cancer Research Organisation GC-08) trial were analysed for sPD-1, sPD-L1 and sCTLA-4. Corresponding baseline clinical data were also retrieved.

Results: Higher plasma levels of sPD-1 (hazard ratio [HR] = 1.27, p = 0.020), sPD-L1 (HR = 1.86, p < 0.001) and sCTLA-4 (HR = 1.33, p = 0.008) were significantly associated with shorter overall survival (OS), whereas only higher sPD-L1 levels was significantly associated with shorter progression-free survival (HR = 1.30, p = 0.008). The sPD-L1 concentration was significantly associated with the Glasgow prognostic score (GPS) (p < 0.001), but both sPD-L1 (HR = 1.67, p < 0.001) and GPS (HR = 1.39, p = 0.009 for GPS 0 versus 1; HR = 1.95, p < 0.001 for GPS 0 versus 2) were independently associated with OS. Patients with a GPS of 0 and low sPD-L1 thus showed the longest OS (median, 12.0 months) and those with a GPS of 2 and high sPD-L1 showed the shortest OS (median, 3.1 months), yielding a HR of 3.69 (p < 0.001).

Conclusion: Baseline sPD-L1 levels have the potential to predict survival for advanced GC patients treated with nivolumab, with the prognostic accuracy of sPD-L1 being improved by its combination with GPS.

Keywords: Gastric cancer; Nivolumab; Soluble CTLA-4; Soluble PD-1; Soluble PD-L1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • B7-H1 Antigen / metabolism
  • Biomarkers, Tumor
  • Humans
  • Ligands
  • Nivolumab* / therapeutic use
  • Prognosis
  • Stomach Neoplasms* / drug therapy


  • Nivolumab
  • Ligands
  • Biomarkers, Tumor
  • B7-H1 Antigen