1318P Association between soluble PD-L1 and prognosis of non-small cell lung cancer (NSCLC) patients treated with immunotherapy

Immune checkpoints inhibitors (ICIs) have revolutionized the treatment of advanced non-small cell lung cancer (NSCLC). PD-L1 expression on tumor specimens is the only approved predictive biomarker (tissue PD-L1, tPD-L1). However, the outcome of patients treated with ICIs is frequently independent from tPD-L1 status; thus, more suitable biomarkers are needed. In this study, we analyzed the role of soluble PD-L1 (sPD-L1) collected from the peripheral blood of patients with advanced NSCLC treated with nivolumab (Nivo) or pembrolizumab (Pembro). We evaluated sPD-L1 in baseline plasma samples withdrawn from 196 advanced NSCLC patients, including 118 patients treated with Nivo in second or further lines (range: 1-6 previous lines), 56 patients with high tissue PD-L1 expression (tPD-L1≥50%) treated with Pembro in first line, and 22 patients with low tissue PD-L1 expression (tPD-L1 <50%) treated with chemotherapy (Chemo); additionally, we evaluated sPD-L1 from 88 healthy donors. sPD-L1 was analyzed with enzyme linked immunosorbent assay (ELISA), by using Dako PD-L1 28-8 pharmDx assay. We explored correlations between sPD-L1 and clinical outcomes of Pembro cohort and Nivo cohort. In addition, we compared sPD-L1 with tPD-L1 in previously untreated patients (Pembro cohort and Chemo cohort). The sPD-L1 median concentration of 23.92 pg/ml was used as cut- off. sPD-L1 level was higher in patients with advanced NSCLC compared to healthy controls (p<0.0001). Moreover, we found higher concentration of sPD-L1 in previously untreated patients with tPD-L1≥50% versus patients with tPD-L1<50% (p= 0.033). In Pembro cohort, median overall survival in low and high sPD-L1 level groups were 16.0 and 10.9 months, respectively (p=0.045). No difference in progression-free survival or objective response was observed. In Nivo cohort, sPD-L1 was not associated with clinical outcomes. Our study shows that baseline sPD-L1 is associated with poor prognosis in advanced NSCLC patients treated with Pembro in first line. sPD-L1 was not prognostic for pre-treated patients receiving Nivo. Additional analyses on longitudinal sPD-L1 assessments are ongoing.