Universität zu Köln

Lyu, Su Ir ORCID: 0009-0002-4125-6048, Fretter, Caroline, Simon, Adrian Georg ORCID: 0000-0002-2709-863X, Spielmann, Sarah-Michele, Damanakis, Alexander I. ORCID: 0000-0002-1155-5541, Zhao, Yue ORCID: 0000-0002-6790-3402, Bruns, Christiane J. ORCID: 0000-0001-6590-8181, Schmidt, Thomas ORCID: 0000-0002-7166-3675, Popp, Felix C. ORCID: 0000-0002-1690-6777, Waldschmidt, Dirk, Quaas, Alexander ORCID: 0000-0002-3537-6011 and Knipper, Karl ORCID: 0009-0008-7133-3538 (2024). Extent and clinical significance of the therapy-relevant tight junction protein Claudin 18.2 in pancreatic ductal adenocarcinoma - real-world evidence. Translational Oncology, 47. pp. 1-6. Elsevier. ISSN 1936-5233

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Abstract

[Artikel-Nr.: 102044] Purpose: Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis, wherefore targeted therapies have experienced increasing interest. Zolbetuximab is a novel targeted therapy under investigation in patients with PDAC and targets Claudin 18.2 (CLDN18.2), which is a component of tight junctions and is of significance in various solid tumors. As its role in PDAC is not definitively elucidated, this study aims to clarify the significance of CLDN18.2 expression in PDAC in a real-world setting. Methods: All patients (n = 309) were recruited at one of the PANCALYZE study centers and received pancreatic resection with curative intention. Paraffin samples were analyzed using an antibody against CLDN18.2, which is known to be comparable to the antibody used by the SPOTLIGHT and GLOW studies. Results: 94 PDACs are positive for CLDN18.2 (30.4 %). Positive CLDN 18.2 expression was associated with significantly better cancer differentiation (p < 0.001). Patients with positive CLDN18.2 expression showed significantly better overall survival when compared to patients with negative expression (median OS: 30 versus 18 months, p = 0.003). Additionally, in multivariable analyses, CLDN18.2 expression was identified as an independent factor for better survival in patients with PDAC (HR = 0.686, 95 %CI = 0.492–0.956, p = 0.026). Conclusion: Significant improvement in survival could be demonstrated by adding Zolbetuximab to known chemotherapy regimes in patients with gastro-esophageal junction adenocarcinoma with at least 75 % CLDN18.2 positive cancer cells. Our findings demonstrate, that 30.4 % of the included patients with PDAC would potentially be eligible for therapy with Zolbetuximab in a real-world patient cohort. Results of trials targeting Claudin 18.2 are pending in patients with PDAC.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Lyu, Su Ir UNSPECIFIED https://orcid.org/0009-0002-4125-6048 UNSPECIFIED Fretter, Caroline UNSPECIFIED UNSPECIFIED UNSPECIFIED Simon, Adrian Georg UNSPECIFIED https://orcid.org/0000-0002-2709-863X UNSPECIFIED Spielmann, Sarah-Michele UNSPECIFIED UNSPECIFIED UNSPECIFIED Damanakis, Alexander I. UNSPECIFIED https://orcid.org/0000-0002-1155-5541 UNSPECIFIED Zhao, Yue UNSPECIFIED https://orcid.org/0000-0002-6790-3402 UNSPECIFIED Bruns, Christiane J. UNSPECIFIED https://orcid.org/0000-0001-6590-8181 UNSPECIFIED Schmidt, Thomas UNSPECIFIED https://orcid.org/0000-0002-7166-3675 UNSPECIFIED Popp, Felix C. UNSPECIFIED https://orcid.org/0000-0002-1690-6777 UNSPECIFIED Waldschmidt, Dirk UNSPECIFIED UNSPECIFIED UNSPECIFIED Quaas, Alexander UNSPECIFIED https://orcid.org/0000-0002-3537-6011 UNSPECIFIED Knipper, Karl UNSPECIFIED https://orcid.org/0009-0008-7133-3538 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-814220
Identification Number:	10.1016/j.tranon.2024.102044
Journal or Publication Title:	Translational Oncology
Volume:	47
Page Range:	pp. 1-6
Number of Pages:	6
Date:	September 2024
Publisher:	Elsevier
ISSN:	1936-5233
Language:	English
Faculty:	Faculty of Medicine
Divisions:	Faculty of Medicine > Chirurgie > Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Transplantationschirurgie Faculty of Medicine > Innere Medizin > Klinik für Gastroenterologie und Hepatologie Faculty of Medicine > Pathologie und Neuropathologie > Institut für Pathologie
Subjects:	Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language Pancreatic ductal adenocarcinoma ; Claudin 18.2 ; Zolbetuximab ; Personalized medicine ; Biomarker English
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/81422