Comprehensive biomarker analysis of long-term response to trastuzumab in patients with HER2-positive advanced gastric or gastroesophageal adenocarcinoma

• Verfasst von: Porth, Isabel [VerfasserIn]
• Verfasst von: Hirsch, Daniela [VerfasserIn]
• Verfasst von: Ceribas, Yonca [VerfasserIn]
• Verfasst von: Weidner, Philip [VerfasserIn]
• Verfasst von: Weichert, Wilko [VerfasserIn]
• Verfasst von: Götze, Thorsten [VerfasserIn]
• Verfasst von: Perner, Sven Roger [VerfasserIn]
• Verfasst von: Luley, Kim [VerfasserIn]
• Verfasst von: Heyer, Christian Moritz [VerfasserIn]
• Verfasst von: Torre, Carolina de la [VerfasserIn]
• Verfasst von: Hofheinz, Ralf-Dieter [VerfasserIn]
• Verfasst von: Lorenzen, Sylvie [VerfasserIn]
• Verfasst von: Gaiser, Timo [VerfasserIn]
• Titel: Comprehensive biomarker analysis of long-term response to trastuzumab in patients with HER2-positive advanced gastric or gastroesophageal adenocarcinoma
• Verf.angabe: Isabel Porth, Daniela Hirsch, Yonca Ceribas, Philip Weidner, Wilko Weichert, Thorsten Oliver Götze, Sven Perner, Kim Luley, Christian Moritz Heyer, Carolina de la Torre, Ralf-Dieter Hofheinz, Sylvie Lorenzen, Timo Gaiser
• E-Jahr: 2023
• Jahr: April 2023
• Umfang: 12 S.
• Fussnoten: Gesehen am 19.05.2023
• Titel Quelle: Enthalten in: European journal of cancer
• Ort Quelle: Amsterdam [u.a.] : Elsevier, 1992
• Jahr Quelle: 2023
• Band/Heft Quelle: 183(2023), Seite 119-130
• ISSN Quelle: 1879-0852
• DOI: doi:10.1016/j.ejca.2023.01.022
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Gastric cancer
• Sach-SW: HER2
• Sach-SW: PD-L1
• Sach-SW: Prognostic factor
• Sach-SW: Trastuzumab
• K10plus-PPN: 1845703448

Abstract

Background - A subgroup of patients with HER2-positive metastatic gastric and gastroesophageal junction cancers shows long-term response under trastuzumab maintenance monotherapy. Obviously, HER2 status alone is not able to identify these patients. We performed this study to identify potential new prognostic biomarkers for this long-term responding patient group. - Patients and methods - Tumour samples of 19 patients with HER2-positive metastatic gastric and gastroesophageal junction cancer who underwent trastuzumab treatment were retrospectively collected from multiple centres. Patients were divided into long-term responding (n = 7) or short-term responding group (n = 12) according to progression-free survival (PFS≥12 months vs. PFS < 12 months). Next-generation sequencing and microarray-based gene expression analysis were performed along with HER2 and PD-L1 immunohistochemistry. - Results - Long-term responding patients had significantly higher PD-L1 combined positive scores (CPS) and CPS correlated with longer progression-free survival. PD-L1 positivity (CPS ≥ 1) was further associated with an increased CD4+ memory T-cell score. The ERBB2 copy number as well as the tumour mutational burden could not discriminate between short-term and long-term responding patients. Genetic alterations and coamplifications in HER2 pathway associated genes such as EGFR, which were connected to trastuzumab resistance, were present in 10% of the patients and equally distributed between the groups. - Conclusion - The study highlights the clinical relevance of PD-L1 testing also in the context of trastuzumab treatment and offers a biological rational by demonstrating elevated CD4+ memory T-cells scores in the PD-L1-positive group.