Analyses of PD-L1 and Inflammatory Gene Expression Association with Efficacy of Nivolumab ± 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. Patients and Methods: In post hoc exploratory analyses from CheckMate 032 (GC/GEJC cohort), we evaluated associations between nivolumab +/- ipilimumab (NIVO +/- 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, x 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 >= 5 and >= 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 >= 5 and >= 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 >= 5 and >= 10) versus PD-L1-negative status. Similar results were observed in the NIVO1 mg/kg+IPI 3 mg/kg subgroup. Multiple inflammatory gene signatures/transcripts, including a signature consisting of four genes (CD274, CD8A, LAG3, and STAT1), showed associations with response to NIVO +/- IPI. Conclusions: This study suggests a greater association of PD-L1 expression by CPS with NIVO +/- IPI efficacy compared with % TC PD-L1 expression in patients with GC/GEJC. Inflammatory signatures were also associated with NIVO +/- IPI response, warranting further investigation.

Automated summary

This study indicates a stronger association between PD-L1 expression determined by CPS and efficacy of immune checkpoint inhibitors in patients with advanced gastric cancer/gastroesophageal junction cancer (GC/GEJC). Inflammatory signatures are also correlated with response to this therapy, suggesting the need for further investigation.