American Association for Cancer Research
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10780432ccr202790-sup-247494_3_supp_6959428_qpd1x0.xlsx (15.68 kB)

Supplementary Table 2 from Analyses of PD-L1 and Inflammatory Gene Expression Association with Efficacy of Nivolumab ± Ipilimumab in Gastric Cancer/Gastroesophageal Junction Cancer

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posted on 2023-03-31, 22:48 authored by 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

Corresponding % TC and CPS with response and OS

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Bristol Myers Squibb

ONO Pharmaceutical Co., Ltd.

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ARTICLE ABSTRACT

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. 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. 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. 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

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