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- W3149557634 abstract "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" @default.
- W3149557634 created "2021-04-13" @default.
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- W3149557634 date "2021-03-29" @default.
- W3149557634 modified "2023-10-11" @default.
- W3149557634 title "Analyses of PD-L1 and Inflammatory Gene Expression Association with Efficacy of Nivolumab ± Ipilimumab in Gastric Cancer/Gastroesophageal Junction Cancer" @default.
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- W3149557634 doi "https://doi.org/10.1158/1078-0432.ccr-20-2790" @default.
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