Analyses of PD-L1 and Inflammatory Gene Expression Association with Efficacy of Nivolumab{plus minus}Ipilimumab in Gastric Cancer/Gastroesophageal Junction Cancer.

Purpose In advanced gastric cancer/gastroesophageal junction cancer (GC/GEJC), there is a need to identify biomarkers of response to therapies, such as immune checkpoint inhibitors. Experimental design In post-hoc exploratory analyses from CheckMate 032 (GC/GEJC cohort), we evaluated associations between nivolumab{plus minus}ipilimumab (NIVO{plus minus}IPI) efficacy and programmed death ligand 1 (PD-L1) expression, defined by tumor cells (% TC) or combined positive score (CPS; sum of PD-L1-staining TCs + immune cells, divided by total viable TCs, × 100) using the Dako PD-L1 IHC 28-8 pharmDx assay, or inflammatory gene expression. Results There was a trend toward increased efficacy (objective response and overall survival) when PD-L1 expression was determined by CPS compared with % TC at higher cutoffs of {greater than or equal to}5 and {greater than or equal to}10 in the pooled analysis of all treatment regimens. In this analysis, 19% and 26% of patients with PD-L1-positive tumors at a CPS cutoff of {greater than or equal to}5 and {greater than or equal to}10, respectively, had an objective response compared with 8% and 9% of patients at the equivalent %TC cutoffs. Longer survival was demonstrated in patients with PD-L1-positive (defined by CPS cutoffs of {greater than or equal to}5 and {greater than or equal to}10) versus PD-L1-negative status. Similar results were observed in the NIVO 1 mg/kg+IPI 3 mg/kg (NIVO1+IPI3) subgroup. Multiple inflammatory gene signatures/transcripts, including a signature consisting of 4 genes (CD274, CD8A, LAG3, and STAT1), showed associations with response to NIVO{plus minus}IPI. Conclusions This study suggests a greater association of PD-L1 expression by CPS with NIVO{plus minus}IPI efficacy compared with %TC PD‑L1 expression in patients with GC/GEJC. Inflammatory signatures were also associated with NIVO{plus minus}IPI response, warranting further investigation.