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

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

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

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 þ 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 þ 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.

Original languageEnglish (US)
Pages (from-to)3925-3935
Number of pages11
JournalClinical Cancer Research
Volume27
Issue number14
DOIs
StatePublished - Jul 15 2021

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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