dc.contributor.author | Lei, M | |
dc.contributor.author | Siemers, NO | |
dc.contributor.author | Pandya, D | |
dc.contributor.author | Chang, H | |
dc.contributor.author | Sanchez, T | |
dc.contributor.author | Harbison, C | |
dc.contributor.author | Szabo, PM | |
dc.contributor.author | Janjigian, Y | |
dc.contributor.author | Ott, PA | |
dc.contributor.author | Sharma, P | |
dc.contributor.author | Bendell, J | |
dc.contributor.author | Evans, TRJ | |
dc.contributor.author | de Braud, F | |
dc.contributor.author | Chau, I | |
dc.contributor.author | Boyd, Z | |
dc.date.accessioned | 2021-06-11T13:13:42Z | |
dc.date.available | 2021-06-11T13:13:42Z | |
dc.date.issued | 2021-03-29 | |
dc.identifier.citation | Clinical cancer research : an official journal of the American Association for Cancer Research, 2021 | |
dc.identifier.issn | 1078-0432 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4636 | |
dc.identifier.eissn | 1557-3265 | |
dc.identifier.doi | 10.1158/1078-0432.ccr-20-2790 | |
dc.description.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. | |
dc.format | Print-Electronic | |
dc.language | eng | |
dc.language.iso | eng | |
dc.rights.uri | https://www.rioxx.net/licenses/all-rights-reserved | |
dc.title | Analyses of PD-L1 and Inflammatory Gene Expression Association with Efficacy of Nivolumab ± Ipilimumab in Gastric Cancer/Gastroesophageal Junction Cancer. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2021-03-24 | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1158/1078-0432.ccr-20-2790 | |
rioxxterms.licenseref.uri | https://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.licenseref.startdate | 2021-03-29 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Clinical cancer research : an official journal of the American Association for Cancer Research | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.publication-status | Published | |
pubs.embargo.terms | Not known | |
dc.contributor.icrauthor | Chau, Ian | |