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

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 p...

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Hauptverfasser: Porth, Isabel (VerfasserIn) , Hirsch, Daniela (VerfasserIn) , Ceribas, Yonca (VerfasserIn) , Weidner, Philip (VerfasserIn) , Weichert, Wilko (VerfasserIn) , Götze, Thorsten (VerfasserIn) , Perner, Sven Roger (VerfasserIn) , Luley, Kim (VerfasserIn) , Heyer, Christian Moritz (VerfasserIn) , Torre, Carolina de la (VerfasserIn) , Hofheinz, Ralf-Dieter (VerfasserIn) , Lorenzen, Sylvie (VerfasserIn) , Gaiser, Timo (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: April 2023
In: European journal of cancer
Year: 2023, Jahrgang: 183, Pages: 119-130
ISSN:1879-0852
DOI:10.1016/j.ejca.2023.01.022
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.ejca.2023.01.022
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0959804923000461
Volltext
Verfasserangaben: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
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 19.05.2023
Beschreibung:Online Resource
ISSN:1879-0852
DOI:10.1016/j.ejca.2023.01.022

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