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

Medientyp: E-Artikel

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

Beteiligte: Porth, Isabel [Verfasser:in]; Hirsch, Daniela [Verfasser:in]; Ceribas, Yonca [Verfasser:in]; Weidner, Philip [Verfasser:in]; Weichert, Wilko [Verfasser:in]; Götze, Thorsten Oliver [Verfasser:in]; Perner, Sven [Verfasser:in]; Luley, Kim [Verfasser:in]; Heyer, Christian Moritz [Verfasser:in]; de la Torre, Carolina [Verfasser:in]; Hofheinz, Ralf-Dieter [Verfasser:in]; Lorenzen, Sylvie [Verfasser:in]; Gaiser, Timo [Verfasser:in]

Erschienen: Augsburg University Publication Server (OPUS), 2023

Sprache: Englisch

DOI: https://doi.org/10.1016/j.ejca.2023.01.022

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Beschreibung: 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 Tumor samples of 19 patients with HER2-positive metastatic gastric and gastroesophageal junction cancer who underwent trastuzumab treatment were retrospectively collected from multiple centers. 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 tumor mutational burden could not discriminate between short-term and long-term responding patients. Genetic alterations and co-amplifications 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.

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