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

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.

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, × 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 NIVO 1 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.See related commentary by Moutafi and Rimm, p. 3812.

• Authors: Ming Lei, Nathan O Siemers, Dimple Pandya, Han Chang, Teresa Sanchez, Christopher Harbison, Peter M Szabo, Yelena Janjigian, Patrick A Ott, Padmanee Sharma, Johanna Bendell, Thomas R Jeffry Evans, Filippo de Braud, Ian Chau, Zachary Boyd
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 27 Issue 14 Pg. 3926-3935 (07 15 2021) ISSN: 1557-3265 [Electronic] United States
• PMID: 33782030 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2021 American Association for Cancer Research.

Chemical References

• Antineoplastic Agents, Immunological
• B7-H1 Antigen
• CD274 protein, human
• Ipilimumab
• Nivolumab

Topics

• Aged
• Antineoplastic Agents, Immunological (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• B7-H1 Antigen (genetics)
• Esophageal Neoplasms (complications, drug therapy, genetics)
• Esophagogastric Junction
• Female
• Humans
• Inflammation (complications, genetics)
• Ipilimumab (administration & dosage)
• Male
• Middle Aged
• Nivolumab (administration & dosage)
• Stomach Neoplasms (complications, drug therapy, genetics)
• Treatment Outcome