Analyses of PD-L1 and inflammatory gene expression association with efficacy of nivolumab±Ipilimumab in gastric cancer/gastroesophageal junction cancer

Lei, M. et al. (2021) Analyses of PD-L1 and inflammatory gene expression association with efficacy of nivolumab±Ipilimumab in gastric cancer/gastroesophageal junction cancer. Clinical Cancer Research, 27(14), pp. 3926-3935. (doi: 10.1158/1078-0432.CCR-20-2790) (PMID:33782030)

Abstract

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Evans, Professor Jeff
• Authors: Lei, M., Siemers, N. O., Pandya, D., Chang, H., Sanchez, T., Harbison, C., Szabo, P. M., Janjigian, Y., Ott, P. A., Sharma, P., Bendell, J., Evans, T. R. J., de Braud, F., Chau, I., and Boyd1, Z.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Clinical Cancer Research
• Publisher: American Association for Cancer Research
• ISSN: 1078-0432
• ISSN (Online): 1557-3265
• Published Online: 29 March 2021
• Copyright Holders: Copyright © 2021 American Association for Cancer Research
• First Published: First published in Clinical Cancer Research 27(14): 3926-3935
• Publisher Policy: Reproduced in accordance with the publisher copyright policy