Cargando…

Comprehensive clinical and molecular characterization of claudin 18.2 expression in advanced gastric or gastroesophageal junction cancer

BACKGROUND: We conducted comprehensive clinical and molecular characterization of claudin 18.2 expression (CLDN18.2) in advanced gastric or gastroesophageal junction cancer (GC/GEJC). PATIENTS AND METHODS: Patients with advanced GC/GEJC who received systemic chemotherapy from October 2015 to Decembe...

Descripción completa

Detalles Bibliográficos
Autores principales: Kubota, Y., Kawazoe, A., Mishima, S., Nakamura, Y., Kotani, D., Kuboki, Y., Bando, H., Kojima, T., Doi, T., Yoshino, T., Kuwata, T., Shitara, K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10024138/
https://www.ncbi.nlm.nih.gov/pubmed/36610262
http://dx.doi.org/10.1016/j.esmoop.2022.100762
_version_ 1784909039501574144
author Kubota, Y.
Kawazoe, A.
Mishima, S.
Nakamura, Y.
Kotani, D.
Kuboki, Y.
Bando, H.
Kojima, T.
Doi, T.
Yoshino, T.
Kuwata, T.
Shitara, K.
author_facet Kubota, Y.
Kawazoe, A.
Mishima, S.
Nakamura, Y.
Kotani, D.
Kuboki, Y.
Bando, H.
Kojima, T.
Doi, T.
Yoshino, T.
Kuwata, T.
Shitara, K.
author_sort Kubota, Y.
collection PubMed
description BACKGROUND: We conducted comprehensive clinical and molecular characterization of claudin 18.2 expression (CLDN18.2) in advanced gastric or gastroesophageal junction cancer (GC/GEJC). PATIENTS AND METHODS: Patients with advanced GC/GEJC who received systemic chemotherapy from October 2015 to December 2019 with available tumor specimens were analyzed. We evaluated clinicopathological features of CLDN18.2 expression with four molecular subtypes: mismatch repair deficient, Epstein–Barr virus-positive, human epidermal growth factor receptor 2-positive, and others. In addition, programmed death-ligand 1 (PD-L1) combined positive score (CPS), genomic alterations, and the expression of immune cell markers were assessed. Clinical outcomes of standard first- or second-line chemotherapy and subsequent anti-programmed cell death protein 1 (anti-PD-1) therapy were also investigated according to CLDN18.2 expression. RESULTS: Among 408 patients, CLDN18.2-positive (moderate-to-strong expression in ≥75%) was identified in 98 patients (24.0%) with almost equal distribution in the four molecular subtypes or CPS subgroups. CLDN18.2-positive was associated with Borrmann type 4, KRAS amplification, low CD16, and high CD68 expression. Overall survival with first-line chemotherapy was not significantly different between CLDN18.2-positive and -negative groups [median 18.4 versus 20.1 months; hazard ratio 1.26 (95% confidence interval 0.89-1.78); P = 0.191] regardless of stratification by PD-L1 CPS ≥5. Progression-free survival and objective response rates of first- and second-line chemotherapy, and anti-PD-1 therapy also showed no significant differences according to CLDN18.2 status. CONCLUSIONS: CLDN18.2 expression in advanced GC/GEJC was associated with some clinical and molecular features but had no impact on treatment outcomes with chemotherapy or checkpoint inhibition. CLDN18.2-positive also had no impact on overall survival. This information could be useful to interpret the results from currently ongoing clinical trials of CLDN18.2-targeted therapies for advanced GC/GEJC and to consider a treatment strategy for CLDN18.2-positive GC/GEJC.
format Online
Article
Text
id pubmed-10024138
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-100241382023-03-19 Comprehensive clinical and molecular characterization of claudin 18.2 expression in advanced gastric or gastroesophageal junction cancer Kubota, Y. Kawazoe, A. Mishima, S. Nakamura, Y. Kotani, D. Kuboki, Y. Bando, H. Kojima, T. Doi, T. Yoshino, T. Kuwata, T. Shitara, K. ESMO Open Original Research BACKGROUND: We conducted comprehensive clinical and molecular characterization of claudin 18.2 expression (CLDN18.2) in advanced gastric or gastroesophageal junction cancer (GC/GEJC). PATIENTS AND METHODS: Patients with advanced GC/GEJC who received systemic chemotherapy from October 2015 to December 2019 with available tumor specimens were analyzed. We evaluated clinicopathological features of CLDN18.2 expression with four molecular subtypes: mismatch repair deficient, Epstein–Barr virus-positive, human epidermal growth factor receptor 2-positive, and others. In addition, programmed death-ligand 1 (PD-L1) combined positive score (CPS), genomic alterations, and the expression of immune cell markers were assessed. Clinical outcomes of standard first- or second-line chemotherapy and subsequent anti-programmed cell death protein 1 (anti-PD-1) therapy were also investigated according to CLDN18.2 expression. RESULTS: Among 408 patients, CLDN18.2-positive (moderate-to-strong expression in ≥75%) was identified in 98 patients (24.0%) with almost equal distribution in the four molecular subtypes or CPS subgroups. CLDN18.2-positive was associated with Borrmann type 4, KRAS amplification, low CD16, and high CD68 expression. Overall survival with first-line chemotherapy was not significantly different between CLDN18.2-positive and -negative groups [median 18.4 versus 20.1 months; hazard ratio 1.26 (95% confidence interval 0.89-1.78); P = 0.191] regardless of stratification by PD-L1 CPS ≥5. Progression-free survival and objective response rates of first- and second-line chemotherapy, and anti-PD-1 therapy also showed no significant differences according to CLDN18.2 status. CONCLUSIONS: CLDN18.2 expression in advanced GC/GEJC was associated with some clinical and molecular features but had no impact on treatment outcomes with chemotherapy or checkpoint inhibition. CLDN18.2-positive also had no impact on overall survival. This information could be useful to interpret the results from currently ongoing clinical trials of CLDN18.2-targeted therapies for advanced GC/GEJC and to consider a treatment strategy for CLDN18.2-positive GC/GEJC. Elsevier 2023-01-05 /pmc/articles/PMC10024138/ /pubmed/36610262 http://dx.doi.org/10.1016/j.esmoop.2022.100762 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Research
Kubota, Y.
Kawazoe, A.
Mishima, S.
Nakamura, Y.
Kotani, D.
Kuboki, Y.
Bando, H.
Kojima, T.
Doi, T.
Yoshino, T.
Kuwata, T.
Shitara, K.
Comprehensive clinical and molecular characterization of claudin 18.2 expression in advanced gastric or gastroesophageal junction cancer
title Comprehensive clinical and molecular characterization of claudin 18.2 expression in advanced gastric or gastroesophageal junction cancer
title_full Comprehensive clinical and molecular characterization of claudin 18.2 expression in advanced gastric or gastroesophageal junction cancer
title_fullStr Comprehensive clinical and molecular characterization of claudin 18.2 expression in advanced gastric or gastroesophageal junction cancer
title_full_unstemmed Comprehensive clinical and molecular characterization of claudin 18.2 expression in advanced gastric or gastroesophageal junction cancer
title_short Comprehensive clinical and molecular characterization of claudin 18.2 expression in advanced gastric or gastroesophageal junction cancer
title_sort comprehensive clinical and molecular characterization of claudin 18.2 expression in advanced gastric or gastroesophageal junction cancer
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10024138/
https://www.ncbi.nlm.nih.gov/pubmed/36610262
http://dx.doi.org/10.1016/j.esmoop.2022.100762
work_keys_str_mv AT kubotay comprehensiveclinicalandmolecularcharacterizationofclaudin182expressioninadvancedgastricorgastroesophagealjunctioncancer
AT kawazoea comprehensiveclinicalandmolecularcharacterizationofclaudin182expressioninadvancedgastricorgastroesophagealjunctioncancer
AT mishimas comprehensiveclinicalandmolecularcharacterizationofclaudin182expressioninadvancedgastricorgastroesophagealjunctioncancer
AT nakamuray comprehensiveclinicalandmolecularcharacterizationofclaudin182expressioninadvancedgastricorgastroesophagealjunctioncancer
AT kotanid comprehensiveclinicalandmolecularcharacterizationofclaudin182expressioninadvancedgastricorgastroesophagealjunctioncancer
AT kubokiy comprehensiveclinicalandmolecularcharacterizationofclaudin182expressioninadvancedgastricorgastroesophagealjunctioncancer
AT bandoh comprehensiveclinicalandmolecularcharacterizationofclaudin182expressioninadvancedgastricorgastroesophagealjunctioncancer
AT kojimat comprehensiveclinicalandmolecularcharacterizationofclaudin182expressioninadvancedgastricorgastroesophagealjunctioncancer
AT doit comprehensiveclinicalandmolecularcharacterizationofclaudin182expressioninadvancedgastricorgastroesophagealjunctioncancer
AT yoshinot comprehensiveclinicalandmolecularcharacterizationofclaudin182expressioninadvancedgastricorgastroesophagealjunctioncancer
AT kuwatat comprehensiveclinicalandmolecularcharacterizationofclaudin182expressioninadvancedgastricorgastroesophagealjunctioncancer
AT shitarak comprehensiveclinicalandmolecularcharacterizationofclaudin182expressioninadvancedgastricorgastroesophagealjunctioncancer