Abstract 4018: Long-term response to Trastuzumab in patients with advanced gastric or gastroesophageal adenocarcinoma - A retrospective study

Abstract

Abstract Since 2010, Trastuzumab combined with chemotherapy is the standard treatment for patients with HER2 (ERBB2) positive advanced or metastatic gastric and gastroesophageal junction cancer (GGEJ). While few patients show long-term response to the treatment, most suffer from rapid disease progression. Several studies revealed that genomic alterations, gene expression changes and altered HER2 signaling activity contribute to impaired therapy response. However, the underlying mechanism remains unclear. The aim of this research project is to analyze differences between patients with long and short progression-free survival by utilizing combined genetic, histologic, clinical and gene expression data. We collected a retrospective German patient cohort (n=20) including patients with HER2 positive advanced GGEJ who received Trastuzumab combined with chemotherapy. Using archival samples that were obtained prior to Trastuzumab treatment, we created a dataset including clinical information, histologic assessment, immunostaining, target amplicon sequencing (TAS; 409 gene panel) and human transcriptome data using the Affymetrix platform. To analyze the TAS sequencing data, we generated an automated analysis pipeline, which detects single nucleotide variants (SNV) and copy number alterations (CNA). Information about genomic alteration will be correlated with pathway and gene set enrichment analysis (GSEA) from the Affymetrix data. Furthermore, the data will be supported by investigating the functional status of HER2 in patient samples via electron microscopy. The results of this study could give insights on how genetic and transcriptomic alterations are connected to long-term Trastuzumab therapy response in HER2 positive GGEJ patients. This could potentially support therapy decision in personalized medicine. Citation Format: Isabel Porth, Philip Weidner, Sylvie Lorenzen, Wilko Weichert, Thorsten Oliver Götze, Sven Perner, Kim Luley, Daniela Hirsch, Ralf-Dieter Hofheinz, Diana B. Peckys, Zahra Mostajeran, Niels de Jonge, Timo Gaiser. Long-term response to Trastuzumab in patients with advanced gastric or gastroesophageal adenocarcinoma - A retrospective study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4018.